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Fujimoto A, Miyazaki K, Yakushijin K, Fujino T, Munakata W, Ejima Y, Maruyama D, Kubota N, Maeda T, Takizawa J, Hiramoto N, Takeuchi M, Sakai R, Fukuhara N, Taguchi S, Asano N, Yamaguchi M, Suzuki R. Improved prognosis of advanced-stage extranodal NK/T-cell lymphoma: results of the NKEA-Next study. Leukemia 2025; 39:909-916. [PMID: 39962328 PMCID: PMC11976271 DOI: 10.1038/s41375-025-02527-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 12/13/2024] [Accepted: 01/28/2025] [Indexed: 04/09/2025]
Abstract
A retrospective study of extranodal natural killer/T-cell lymphoma (ENKL) patients diagnosed between 2014 and 2021 in Japan was conducted. Among 351 patients with sufficient data, 116 (33%) were in the advanced stage (5 in stage III and 111 in stage IV) at diagnosis, and were further analyzed. The median age was 60 years (range: 19-90), and 68 (59%) were male. Ninety-four (85%) of stage IV patients had two or more extranodal involvements. The most common first-line regimen was SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide; 52%). The 2-year overall survival (OS) for all patients was 38.5%, which was significantly improved after 2017 (25.2% for 2014-2017 vs. 50.7% for 2018-2021; P = 0.008). Patients treated with SMILE showed better OS than those treated with DeVIC or CHOP (2y-OS: 57.1%, 35.8%, and 0%, respectively; P < 0.001). The prognosis was significantly better in patients who received hematopoietic stem cell transplantation (HSCT) than in those who did not (2-year OS: 68.3% vs. 17.6%, P < 0.001). Multivariate analysis showed SMILE and HSCT were significant factors for OS. In conclusion, the prognosis of advanced-stage ENKL has improved in recent years. The L-asparaginase-containing chemotherapy and subsequent HSCT is considered the recommended strategy.
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Affiliation(s)
- Ayumi Fujimoto
- Division of Hematology and Oncology, Department of Internal Medicine, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kana Miyazaki
- Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Kimikazu Yakushijin
- Division of Medical Oncology and Hematology, Department of Medicine, Kobe University Hospital, Kobe, Japan
| | - Takahiro Fujino
- Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Wataru Munakata
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Yasuo Ejima
- Department of Radiology, Dokkyo Medical University, Shimotsuga, Japan
| | - Dai Maruyama
- Department of Hematology Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Nobuko Kubota
- Division of Hematology, Saitama Cancer Center, Ina, Japan
| | - Takeshi Maeda
- Department of Hematology and Oncology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Jun Takizawa
- Department of Hematology, Endocrinology and Metabolism, Faculty of Medicine, Niigata University, Niigata, Japan
| | - Nobuhiro Hiramoto
- Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan
| | | | - Rika Sakai
- Department of Hematology and Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan
| | - Noriko Fukuhara
- Department of Hematology, Tohoku University Hospital, Sendai, Japan
| | - Senzo Taguchi
- Department of Radiation Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoko Asano
- Department of Molecular Diagnostics, Nagano Prefectural Shinshu Medical Center, Suzaka, Japan
| | - Motoko Yamaguchi
- Department of Hematological Malignancies, Mie University Graduate School of Medicine, Tsu, Japan
| | - Ritsuro Suzuki
- Division of Hematology and Oncology, Department of Internal Medicine, Faculty of Medicine, Shimane University, Izumo, Japan.
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Fang X, Zhou F, Ye S, Zhang H, Guo H, Chen X, Liang C, Pu X, Cao Y, Ren Q, Li X, Zhai L, Huang H, Hong H. A prognostic index for advanced-stage extranodal natural killer/T-cell lymphoma: A multicenter study. Ann Hematol 2025; 104:445-455. [PMID: 39774927 DOI: 10.1007/s00277-024-06160-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 12/20/2024] [Indexed: 01/11/2025]
Abstract
Advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL) is a highly heterogeneous disease with very poor prognosis. All commonly utilized prognostic models incorporated both early-stage and advanced-stage patients in the modeling process. This study aim to design a prognostic model specifically for advanced-stage ENKTL, providing risk stratification in affected patients. We analyzed 291 patients with stage III/IV ENKTL receiving asparaginase-based chemotherapy from 8 institutions to develop a new prognostic model and validate it in an independent cohort consisted of 221 patients from 4 additional hospitals. The prognostic model included three independent variables based on a multivariate analysis for overall survival (OS): age, bone marrow invasiveness and visceral organ involvement. We identified three different risk groups: group 1, no adverse factors; group 2, one factor; and group 3, two or three factors, which were associated with 5-year OS rates of 66.0%, 32.3%, and 20.0%, respectively (P < 0.001). The prognostic index of natural killer lymphoma (PINK) and nomogram-revised risk index (NRI) were unsatisfactory for stratifying these patients. These results were validated and confirmed in an independent cohort. This newly proposed model can be used to guide risk-adapted treatment for advanced stage ENKTL.
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Affiliation(s)
- Xiaojie Fang
- Department of Medical Oncology, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Fenglan Zhou
- Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, 610042, China
| | - Sheng Ye
- Department of Medical Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Hongyu Zhang
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Hongqiang Guo
- Department of Medical Oncology, He Nan Cancer Hospital, Zhengzhou, China
| | - Xinggui Chen
- Department of Medical Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Chaoyong Liang
- Department of Medical Oncology, Guangxi Cancer Hospital, Nanning, China
| | - Xingxiang Pu
- Department of Medical Oncology, Hunan Cancer Hospital, Changsha, China
| | - Yabing Cao
- Department of Medical Oncology, Kiang Wu Hospital, Macau, China
| | - Quanguang Ren
- Department of Medical Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoqian Li
- Department of Medical Oncology, Shandong Cancer Hospital, Jinan, China
| | - Linzhu Zhai
- Department of Medical Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - He Huang
- Department of Medical Oncology, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Huangming Hong
- Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, 610042, China.
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Dokhanchi M, Javaherdehi AP, Raad M, Khalilollah S, Mahdavi P, Razizadeh MH, Zafarani A. Natural Killer Cells in Cancers of Respiratory System and Their Applications in Therapeutic Approaches. Immun Inflamm Dis 2024; 12:e70079. [PMID: 39588940 PMCID: PMC11590036 DOI: 10.1002/iid3.70079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 10/29/2024] [Accepted: 11/07/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND Cancer is still regarded as a major worldwide health issue due to its high health and socioeconomic burden. Currently, lung cancer is the most common cause of cancer-related fatalities globally. Additionally, mesotheliomas and other cancers of the respiratory system, including those of the trachea, larynx, and bronchi, are also posing a significant health threat. Natural killer (NK) cells are lymphocytes of the innate immune system involved in response against cancer. OBJECTIVE This review discussed recent findings in the context of NK cell activity in the immune surveillance of respiratory system cancers and NK cell-based treatments to combat those malignancies. RESULTS The presence of natural killer cells in the tumor microenvironment is shown to be associated with a higher survival rate in patients with various malignancies. However, cancerous cells benefit from several mechanisms to evade natural killer cell-mediated cytotoxicity, including reduced major histocompatibility complex I expression, shedding of ligands, upregulation of inhibitory receptors, and release of soluble factors. Using NK cells to design therapeutic approaches may enhance antitumor immunity and improve clinical outcomes. Clinical trials investigating the use of natural killer cells in combination with cytokine stimulation or immune checkpoint inhibitors have exhibited promising results in various respiratory system malignancies. CONCLUSION Respiratory system cancers present significant health challenges worldwide, and while NK cells play a crucial role in tumor surveillance, tumors often evade NK cell responses through various mechanisms. Advances in NK cell-based therapies, including CAR-NK cells, immune checkpoint inhibitors, and cytokine stimulation, have shown promising outcomes in tackling these tactics. However, challenges such as the immunosuppressive tumor microenvironment persist. Ongoing research is crucial to improve NK cell therapies by targeting autophagy, modulating miRNAs, and developing combinatorial approaches to enhance treatment efficacy for respiratory cancers.
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Affiliation(s)
- Maryam Dokhanchi
- Department of Biology, Science and Research BranchIslamic Azad UniversityTehranIran
| | | | - Mohammad Raad
- Department of Molecular, Cellular and Biomedical SciencesUniversity of New HampshireDurhamNew HampshireUSA
| | - Shayan Khalilollah
- School of Medicine, Tehran Medical SciencesIslamic Azad UniversityTehranIran
| | - Pooya Mahdavi
- College of Public HealthUniversity of South FloridaTampaFloridaUSA
| | - Mohammad Hossein Razizadeh
- Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious DiseasesIran University of Medical SciencesTehranIran
| | - Alireza Zafarani
- Cellular and Molecular Research CenterIran University of Medical SciencesTehranIran
- Department of Hematology & Blood Banking, School of Allied MedicineIran University of Medical SciencesTehranIran
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Shen Z, Zhang X, Li Y, Chen X, Xing X, Zhang H, Ye J, Wang L, Jia T, Zhu T, Miao Y, Wang C, Liu H, Wang L, Sang W. A novel prognostic index for extranodal natural killer/T-cell lymphoma in the era of pegaspargase/L-asparaginase. Future Oncol 2024; 20:2071-2081. [PMID: 39041580 PMCID: PMC11497977 DOI: 10.1080/14796694.2024.2376512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 07/02/2024] [Indexed: 07/24/2024] Open
Abstract
Aim: This multicenter retrospective study aimed to develop a novel prognostic system for extranodal natural killer/T-cell lymphoma (ENKTL) patients in the era of pegaspargase/L-asparaginase.Materials & methods: A total of 844 newly diagnosed ENKTL patients were included.Results: Multivariable analysis confirmed that Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, Chinese Southwest Oncology Group and Asia Lymphoma Study Group ENKTL (CA) system, and albumin were independent prognostic factors. By rounding up the hazard ratios from four significant variables, a maximum of 7 points were assigned. The model of Huaihai Lymphoma Working Group-Natural killer/T-cell Lymphoma prognostic index (NPI) was identified with four risk groups and the 5-year overall survival was 88.2, 66.7, 54.3 and 30.5%, respectively.Conclusion: Huaihai Lymphoma Working Group-NPI provides a feasible stratification system for patients with ENKTL in the era of pegaspargase/L-asparaginase.
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Affiliation(s)
- Ziyuan Shen
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China
- Department of Epidemiology & Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China
| | - Xudong Zhang
- Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Yujie Li
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China
| | - Xicheng Chen
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China
| | - Xing Xing
- Department of Epidemiology & Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China
| | - Hao Zhang
- Department of Hematology, The Affiliated Hospital of Jining Medical University, Jining, Shandong, 272000, China
| | - Jingjing Ye
- Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China
| | - Ling Wang
- Department of Hematology, Tai'an Central Hospital, Tai'an, Shandong, 271000, China
| | - Tao Jia
- Department of Hematology, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, 222061, China
| | - Taigang Zhu
- Department of Hematology, The General Hospital of Wanbei Coal-Electric Group, Suzhou, Anhui, 234011, China
| | - Yuqing Miao
- Department of Hematology, Yancheng First People's Hospital, Yancheng, Jiangsu, 224001, China
| | - Chunling Wang
- Department of Hematology, The First People's Hospital of Huai'an, Huai'an, Jiangsu, 223300, China
| | - Hui Liu
- Department of Pathology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China
| | - Liang Wang
- Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100005, China
| | - Wei Sang
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China
- Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu, 221006, China
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Luo Y, Huang Z, Gao Z, Wang B, Zhang Y, Bai Y, Wu Q, Wang M. Prognostic Value of 18F-FDG PET/CT Radiomics in Extranodal Nasal-Type NK/T Cell Lymphoma. Korean J Radiol 2024; 25:189-198. [PMID: 38288898 PMCID: PMC10831304 DOI: 10.3348/kjr.2023.0618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 11/08/2023] [Accepted: 11/16/2023] [Indexed: 02/01/2024] Open
Abstract
OBJECTIVE To investigate the prognostic utility of radiomics features extracted from 18F-fluorodeoxyglucose (FDG) PET/CT combined with clinical factors and metabolic parameters in predicting progression-free survival (PFS) and overall survival (OS) in individuals diagnosed with extranodal nasal-type NK/T cell lymphoma (ENKTCL). MATERIALS AND METHODS A total of 126 adults with ENKTCL who underwent 18F-FDG PET/CT examination before treatment were retrospectively included and randomly divided into training (n = 88) and validation cohorts (n = 38) at a ratio of 7:3. Least absolute shrinkage and selection operation Cox regression analysis was used to select the best radiomics features and calculate each patient's radiomics scores (RadPFS and RadOS). Kaplan-Meier curve and Log-rank test were used to compare survival between patient groups risk-stratified by the radiomics scores. Various models to predict PFS and OS were constructed, including clinical, metabolic, clinical + metabolic, and clinical + metabolic + radiomics models. The discriminative ability of each model was evaluated using Harrell's C index. The performance of each model in predicting PFS and OS for 1-, 3-, and 5-years was evaluated using the time-dependent receiver operating characteristic (ROC) curve. RESULTS Kaplan-Meier curve analysis demonstrated that the radiomics scores effectively identified high- and low-risk patients (all P < 0.05). Multivariable Cox analysis showed that the Ann Arbor stage, maximum standardized uptake value (SUVmax), and RadPFS were independent risk factors associated with PFS. Further, β2-microglobulin, Eastern Cooperative Oncology Group performance status score, SUVmax, and RadOS were independent risk factors for OS. The clinical + metabolic + radiomics model exhibited the greatest discriminative ability for both PFS (Harrell's C-index: 0.805 in the validation cohort) and OS (Harrell's C-index: 0.833 in the validation cohort). The time-dependent ROC analysis indicated that the clinical + metabolic + radiomics model had the best predictive performance. CONCLUSION The PET/CT-based clinical + metabolic + radiomics model can enhance prognostication among patients with ENKTCL and may be a non-invasive and efficient risk stratification tool for clinical practice.
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Affiliation(s)
- Yu Luo
- Department of Medical Imaging, Henan Provincial People's Hospital, The People's Hospital of Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Zhun Huang
- Department of Medical Imaging, Henan Provincial People's Hospital, The People's Hospital of Zhengzhou University, Zhengzhou, China
| | - Zihan Gao
- Department of Medical Imaging, Henan Provincial People's Hospital, The People's Hospital of Zhengzhou University, Zhengzhou, China
| | - Bingbing Wang
- Department of Medical Imaging, Henan Provincial People's Hospital, The People's Hospital of Zhengzhou University, Zhengzhou, China
| | - Yanwei Zhang
- Department of Bethune International Peace Hospital, Department of Radiology, Shijiazhuang, China
| | - Yan Bai
- Department of Medical Imaging, Henan Provincial People's Hospital, The People's Hospital of Zhengzhou University, Zhengzhou, China
| | - Qingxia Wu
- Beijing United Imaging Research Institute of Intelligent Imaging, Beijing, China
| | - Meiyun Wang
- Department of Medical Imaging, Henan Provincial People's Hospital, The People's Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory for Medical Imaging of Neurological Diseases, Zhengzhou, China
- Laboratory of Brain Science and Brain-Like Intelligence Technology, Institute for Integrated Medical Science and Engineering, Henan Academy of Sciences, Zhengzhou, China.
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Sato S, Ishii M, Tachibana K, Furukawa Y, Toyota T, Kinoshita S, Azusawa Y, Ando J, Ando M. Establishment of ganglioside GD2-expressing extranodal NK/T-cell lymphoma cell line with scRNA-seq analysis. Exp Hematol 2024; 130:104132. [PMID: 38029851 DOI: 10.1016/j.exphem.2023.11.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 11/14/2023] [Accepted: 11/19/2023] [Indexed: 12/01/2023]
Abstract
Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL), is characterized by Epstein-Barr virus infection and poor prognosis. We established a novel cell line, ENKL-J1, from bone marrow cells of an ENKL patient. We found that ENKL-J1 cells express the ganglioside GD2 (GD2) and that GD2-directed chimeric antigen receptor T cells exhibit cytotoxicity against ENKL-J1 cells, indicating that GD2 would be a suitable target of GD2-expressing ENKL cells. Targeted next-generation sequencing revealed TP53 and TET2 variants in ENKL-J1 cells. Furthermore, single-cell RNA sequencing in ENKL-J1 cells showed high gene-expression levels in the oncogenic signaling pathways JAK-STAT, NF-κB, and MAPK. Genes related to multidrug resistance (ABCC1), tumor suppression (ATG5, CRYBG1, FOXO3, TP53, MGA), anti-apoptosis (BCL2, BCL2L1), immune checkpoints (CD274, CD47), and epigenetic regulation (DDX3X, EZH2, HDAC2/3) also were expressed at high levels. The molecular targeting agents eprenetapopt, tazemetostat, and vorinostat efficiently induced apoptosis in ENKL-J1 cells in vitro. Furthermore, GD2-directed chimeric antigen receptor T cells showed cytotoxicity against ENKL-J1 cells in vivo. These findings not only contribute to understanding the molecular and genomic characteristics of ENKL; they also suggest new treatment options for patients with advanced or relapsed ENKL.
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Affiliation(s)
- Shoko Sato
- Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Midori Ishii
- Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Kota Tachibana
- Division of Cell Therapy & Blood Transfusion Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Yoshiki Furukawa
- Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Tokuko Toyota
- Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Shintaro Kinoshita
- Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Yoko Azusawa
- Division of Cell Therapy & Blood Transfusion Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Jun Ando
- Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; Division of Cell Therapy & Blood Transfusion Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Miki Ando
- Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
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Chen NC, Chang H, Kuo MC, Lin TL, Shih LY, Chuang WY, Kao HW. Predictive model for treatment outcomes of peripheral T-cell lymphoma, not otherwise specified, in Taiwanese patients. J Formos Med Assoc 2024; 123:188-197. [PMID: 37558588 DOI: 10.1016/j.jfma.2023.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 06/11/2023] [Accepted: 07/20/2023] [Indexed: 08/11/2023] Open
Abstract
PURPOSE We aimed to explore the clinical outcomes and prognostic factors for PTCL-NOS patients in the real world. METHODS Clinical data were retrospectively collected from adult patients with PTCL-NOS treated at a single center in Taiwan. RESULTS 104 PTCL-NOS patients with a median age of 53.0 years were enrolled. Patients with the International Prognostic Index (IPI) or prognostic index for peripheral T-cell lymphoma (PIT) scores of zero had a longer overall survival (OS) and progression free survival (PFS), while patients with IPI or PIT scores ≥1 did poorly. For patients who are eligible for transplantation, the use of pralatrexate as salvage chemotherapy has shown better OS (2-year OS 83.3% vs. 24.4%, P = 0.011) compared to patients who did not. By multivariate analysis, age >60 years, male, B symptoms, ECOG >1, lung involvement, and thrombocytopenia were independent adverse factors for OS. Incorporating factors in multivariate analysis, we established a novel predictive index for PTCL-NOS which efficiently stratifies patients into low (0-1 factor), intermediate-1 (2 factors), intermediate-2 (3 factors), and high risk (4-6 factors) groups with 2-year OS rates of 81.5%, 32.9%, 8.8%, and 0%, respectively (P < 0.001). CONCLUSION PTCL-NOS patients have a dismal prognosis in Taiwan. Novel agents may improve the outcomes of PTCL-NOS patients. The usefulness of the novel prognostic index for PTCL-NOS needs further validation.
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Affiliation(s)
- Ning-Chun Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Hung Chang
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Chung Kuo
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tung-Liang Lin
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Lee-Yung Shih
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wen-Yu Chuang
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Anatomic Pathology, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Hsiao-Wen Kao
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taiwan.
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Wei YC, Liu WX, Qi F, Zhang CG, Zheng BM, Xie Y, Chen B, Zhang D, Liu WP, Fang H, Chai Y, Qi SN, Li YX, Wang WH, Song YQ, Zhu J, Dong M. Clinical features, prognostic stratification, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma: a multi-institutional real-world study. Ann Hematol 2024; 103:163-174. [PMID: 37817010 DOI: 10.1007/s00277-023-05455-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 09/14/2023] [Indexed: 10/12/2023]
Abstract
The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.
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Affiliation(s)
- Yu-Ce Wei
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Wei-Xin Liu
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Fei Qi
- Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Haidian District, No. 52, Fucheng Road, Beijing, 100142, China
| | - Chang-Gong Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Bao-Min Zheng
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Yan Xie
- Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Haidian District, No. 52, Fucheng Road, Beijing, 100142, China
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Di Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Wei-Ping Liu
- Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Haidian District, No. 52, Fucheng Road, Beijing, 100142, China
| | - Hui Fang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue Chai
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Shu-Nan Qi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ye-Xiong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei-Hu Wang
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Yu-Qin Song
- Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Haidian District, No. 52, Fucheng Road, Beijing, 100142, China.
| | - Jun Zhu
- Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Haidian District, No. 52, Fucheng Road, Beijing, 100142, China.
| | - Mei Dong
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
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9
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Nakamura T, Tatetsu H, Higuchi Y, Endo S, Shiraishi S, Kawanaka K, Imakane D, Sonoda M, Furuta R, Shichijo T, Honda Y, Karube K, Mikami Y, Nosaka K, Matsuoka M, Yasunaga JI. Extranodal NK/T-cell lymphoma with localized relapse in bone marrow of lower leg detected using PET-CT. J Clin Exp Hematop 2024; 64:45-51. [PMID: 38538318 PMCID: PMC11079990 DOI: 10.3960/jslrt.23046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 11/27/2023] [Accepted: 12/27/2023] [Indexed: 05/12/2024] Open
Abstract
Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma (NHL) with poor prognosis, particularly in relapsed or refractory patients. Thus, timely detection of relapse and appropriate disease management are crucial. We present two patients with ENKTL, wherein positron emission tomography-computed tomography (PET-CT) with total-body coverage after induction therapy, detected newly relapsed regions in the bone marrow of the lower leg prior to progression. Case 1: A 47-year-old woman with nasal obstruction, showing 18F-fluoro-deoxyglucose (FDG) uptake in the nasal cavity (Lugano stage IE). After induction therapy (RT-2/3 DeVIC), PET-CT revealed abnormal uptake only in the right fibula. Case 2: A 68-year-old man with a skin nodule/ulcer and an enlarged right inguinal lymph node was diagnosed with advanced ENKTL. A PET-CT scan revealed abnormal uptake in the subcutaneous mass of the right medial thigh, lymph nodes, and descending colon (Lugano stage IV). After induction therapy, PET-CT revealed new abnormal uptake only in the left tibia. In both patients, CT-guided biopsy confirmed ENKTL recurrence. Moreover, PET-CT with whole-body coverage was useful for the timely assessment of relapse and detection of asymptomatic bone involvement. This approach allowed for modifications to treatment strategies in certain patients.
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10
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Le MK, Oishi N, Satou A, Miyaoka M, Kawashima I, Mochizuki K, Kirito K, Feldman AL, Nakamura N, Kondo T. Molecular and clinicopathological features of granzyme B-negative extranodal NK/T-cell lymphoma. Hum Pathol 2024; 143:10-16. [PMID: 38000677 DOI: 10.1016/j.humpath.2023.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 11/13/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023]
Abstract
Extranodal NK/T-cell lymphoma (ENKTL) generally expresses cytotoxic molecules, including granzyme B (GZMB), T-cell-restricted intracellular antigen-1 (TIA-1), and perforin; however, the expression of these molecules varies across cases. We performed gene expression profiling and identified unique biological and clinicopathological features of GZMB-negative ENKTL. We reviewed the clinicopathological characteristics of 71 ENKTL samples. Gene expression profiling on nine ENKTLs using multiplexed, direct, and digital mRNA quantification divided ENKTLs into Groups A (n = 7) and B (n = 2) through hierarchical clustering and t-distributed stochastic neighbor embedding. Group B was characterized by downregulation of genes associated with IL6-JAK-STAT3 signaling and inflammatory responses. GZMB mRNA expression was significantly downregulated in Group B. GZMB protein expression was evaluated with immunohistochemistry in all 71 ENKTLs, and expression data of Tyr705-phosphorylated STAT3 (pSTAT3) and MYC from our previous study was utilized. T-cell receptor gamma (TRG) gene rearrangement in the selected samples was also assessed using PCR. GZMB expression was higher in pSTAT3-positive (p = 0.028) and MYC-positive (p = 0.014) ENKTLs. Eighteen percent (13/71) of all ENKTLs were negative for GZMB (defined by positivity <10 %); patients with GZMB-negative ENKTLs were often in a higher clinical stage (p = 0.016). We observed no other correlations with clinical parameters or TRG rearrangement and no significant association between GZMB expression and survival. In conclusion, GZMB expression is highly heterogeneous in ENKTLs and is associated with the activation of the JAK-STAT3 pathway and higher MYC expression. GZMB-negative ENKTLs correlate with an advanced clinical stage, suggesting the potential utility of GZMB immunohistochemistry as a biomarker of ENKTL.
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Affiliation(s)
- Minh-Khang Le
- Department of Pathology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Naoki Oishi
- Department of Pathology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
| | - Akira Satou
- Department of Surgical Pathology, Aichi Medical University Hospital, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Masashi Miyaoka
- Department of Pathology, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Ichiro Kawashima
- Department of Hematology and Oncology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Kunio Mochizuki
- Department of Pathology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Keita Kirito
- Department of Hematology and Oncology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Andrew L Feldman
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Naoya Nakamura
- Department of Pathology, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Tetsuo Kondo
- Department of Pathology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
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11
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Hayashino K, Yoshida C, Ayata Y, Yukawa R, Komura A, Nakamura M, Meguri Y, Yamamoto K, Oda W, Imajo K. Extranodal natural killer/T-cell lymphoma coexisting with peripheral T-cell lymphoma, not otherwise specified. J Clin Exp Hematop 2024; 64:52-58. [PMID: 38538319 PMCID: PMC11079987 DOI: 10.3960/jslrt.23049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 01/18/2024] [Accepted: 01/19/2024] [Indexed: 05/12/2024] Open
Abstract
We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive for CD3 and CD5 and negative for CD56 and Epstein-Barr virus (EBV)-encoded small RNA (EBER) by in situ hybridization. CD4-positive cells and CD8-positive cells were mixed in almost equal numbers. He was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). The patient received one cycle of chemotherapy, resulting in severe sepsis. While undergoing treatment in the intensive care unit with an antimicrobial agent and prednisone, ascitic fluid appeared. Abdominal aspiration revealed neutrophil-predominant ascites and microbiological studies revealed Candida albicans. However, ascites did not improve when treated with micafungin for Candida peritonitis. Abdominal aspiration was re-performed, and atypical lymphoid cells that were positive for CD3 and CD56 were detected. EBV-DNA levels in whole blood were significantly elevated. Atypical lymphoid cells were positive for EBER by in situ hybridization and Southern blot analysis showed EBV terminal repeat monoclonal patterns. Bone marrow examination revealed the same atypical lymphoid cells. Therefore, the patient was diagnosed with extranodal natural killer/T-cell lymphoma (ENKTL) with bone marrow involvement 3 months after the diagnosis of PTCL-NOS. Complications associated with PTCL-NOS and ENKTL are rare. PTCL-NOS, chemotherapy, sepsis, and prednisone might have led to immunodeficiency and reactivation of EBV, which might be one of the pathophysiologies for developing ENKTL. Our case indicates that measuring EBV-DNA in the blood is a simple and prompt examination to detect complications of EBV-associated lymphoma.
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MESH Headings
- Male
- Humans
- Middle Aged
- Epstein-Barr Virus Infections/complications
- Herpesvirus 4, Human
- Lymphoma, T-Cell, Peripheral/complications
- Lymphoma, T-Cell, Peripheral/diagnosis
- Lymphoma, T-Cell, Peripheral/drug therapy
- Prednisone
- Lymphoma, Extranodal NK-T-Cell/complications
- Lymphoma, Extranodal NK-T-Cell/diagnosis
- Ascites/complications
- Ascites/pathology
- Killer Cells, Natural/pathology
- DNA
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12
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Li Y, Luo C, Jiang J, He S, Liu Y, Yan W, Xia Y, Cui Q, Huang Y, Lim JQ, Huang D, Hussein IN, Gao Y, Lin G, Ling Y, Ma D, Zhang Y, Chan JY, Wei P, Wang X, Cheng CL, Xiong J, Zhao W, Ong CK, Lim ST, Huang H, Peng R, Bei J. Single-Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T-Cell Lymphoma. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2303913. [PMID: 37949673 PMCID: PMC10754138 DOI: 10.1002/advs.202303913] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 09/20/2023] [Indexed: 11/12/2023]
Abstract
Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein-Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single-cell RNA sequencing (scRNA-seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single-cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV-encoded genes and low infiltration of tumor-associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single-cell resolution, highlighting the crucial role of malignant NK cells with EBV-encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL.
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Affiliation(s)
- Yi‐Qi Li
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Chun‐Ling Luo
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Jia‐Xin Jiang
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Shuai He
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Yang Liu
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Wen‐Xin Yan
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Yi Xia
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Qian Cui
- Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou510080China
| | - Ying Huang
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Jing Quan Lim
- Lymphoma Translational Research LaboratoryCellular and Molecular ResearchNational Cancer Centre Singapore30 Hospital BoulevardSingapore168583Singapore
- ONCO‐ACPDuke‐NUS Medical School8 College RoadSingapore169857Singapore
| | - Dachuan Huang
- Lymphoma Translational Research LaboratoryCellular and Molecular ResearchNational Cancer Centre Singapore30 Hospital BoulevardSingapore168583Singapore
- ONCO‐ACPDuke‐NUS Medical School8 College RoadSingapore169857Singapore
| | - Izzah Nabilah Hussein
- Lymphoma Translational Research LaboratoryCellular and Molecular ResearchNational Cancer Centre Singapore30 Hospital BoulevardSingapore168583Singapore
| | - Yan Gao
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Guo‐Wang Lin
- Microbiome Medicine CenterDivision of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou510280China
| | - Yi‐Hong Ling
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Dong Ma
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Yue‐Tong Zhang
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Jason Yongsheng Chan
- Division of Medical OncologyNational Cancer Centre Singapore30 Hospital BoulevardSingapore168583Singapore
| | - Pan‐Pan Wei
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Xiao‐Xiao Wang
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Chee Leong Cheng
- Department of PathologySingapore General Hospital20 College RoadAcademia169856Singapore
| | - Jie Xiong
- State Key Laboratory of Medical GenomicsShanghai Institute of HematologyNational Research Center for Translational MedicineShanghai Rui Jin HospitalShanghai Jiao Tong University School of Medicine197 Rui Jin Er RoadShanghai200025China
| | - Wei‐Li Zhao
- State Key Laboratory of Medical GenomicsShanghai Institute of HematologyNational Research Center for Translational MedicineShanghai Rui Jin HospitalShanghai Jiao Tong University School of Medicine197 Rui Jin Er RoadShanghai200025China
| | - Choon Kiat Ong
- Lymphoma Translational Research LaboratoryCellular and Molecular ResearchNational Cancer Centre Singapore30 Hospital BoulevardSingapore168583Singapore
- Cancer and Stem Cell BiologyDuke‐NUS Medical School8 College RoadSingapore169857Singapore
| | - Soon Thye Lim
- Director's OfficeNational Cancer Centre Singapore30 Hospital BoulevardSingapore168583Singapore
- Office of EducationDuke‐NUS Medical SchoolSingapore169857Singapore
| | - Hui‐Qiang Huang
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Rou‐Jun Peng
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Jin‐Xin Bei
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhou510060China
- Lymphoma Translational Research LaboratoryCellular and Molecular ResearchNational Cancer Centre Singapore30 Hospital BoulevardSingapore168583Singapore
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13
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Chávez Dávila YN, Pinos León VH, Tello Astudillo S, Loza Erazo GM, Granizo Rubio JD. Extranodal NK/T-Cell Lymphoma, Nasal Type, Extranasal and Ulcerative Blister Variant, Case Report. Ann Dermatol 2023; 35:S304-S309. [PMID: 38061727 PMCID: PMC10727907 DOI: 10.5021/ad.21.317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 06/23/2022] [Accepted: 01/12/2023] [Indexed: 12/20/2023] Open
Abstract
The extranodal natural killer (NK) T-cell lymphoma of nasal type is a form of lymphoma that falls within the WHO/EORTC 2018 classification of cutaneous T-cell lymphomas. It is characterized for being aggressive, infrequent, and destroying midline facial structures; however, it can also be in primary or secondary form at extranasal sites, such as the skin or the gastrointestinal tract, among others. We report the case of an 18-year-old patient with an extranodal NK/T-cell lymphoma located in an extranasal site. The clinical presentation is characterized for being multifocal and with erythematous-violaceous plaques that progress to hemorrhagic blisters and necrotic ulcers. Although this type of lymphoma has been reported previously by others, the presence of blisters is an atypical finding, which we believe has been described only in one case in the medical literature.
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14
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Liu H, Liu M, Tian X, Wang H, Gao J, Li H, Zhao Z, Liu Y, Liu C, Chen X, Yang Y. Discovery and biological evaluation of a potent small molecule CRM1 inhibitor for its selective ablation of extranodal NK/T cell lymphoma. eLife 2023; 12:e80625. [PMID: 37888961 PMCID: PMC10637774 DOI: 10.7554/elife.80625] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 10/24/2023] [Indexed: 10/28/2023] Open
Abstract
Background The overactivation of NF-κB signaling is a key hallmark for the pathogenesis of extranodal natural killer/T cell lymphoma (ENKTL), a very aggressive subtype of non-Hodgkin's lymphoma yet with rather limited control strategies. Previously, we found that the dysregulated exportin-1 (also known as CRM1) is mainly responsible for tumor cells to evade apoptosis and promote tumor-associated pathways such as NF-κB signaling. Methods Herein we reported the discovery and biological evaluation of a potent small molecule CRM1 inhibitor, LFS-1107. We validated that CRM1 is a major cellular target of LFS-1107 by biolayer interferometry assay (BLI) and the knockdown of CRM1 conferred tumor cells with resistance to LFS-1107. Results We found that LFS-1107 can strongly suppresses the growth of ENKTL cells at low-range nanomolar concentration yet with minimal effects on human platelets and healthy peripheral blood mononuclear cells. Treatment of ENKTL cells with LFS-1107 resulted in the nuclear retention of IkBα and consequent strong suppression of NF-κB transcriptional activities, NF-κB target genes downregulation and attenuated tumor cell growth and proliferation. Furthermore, LFS-1107 exhibited potent activities when administered to immunodeficient mice engrafted with human ENKTL cells. Conclusions Therefore, LFS-1107 holds great promise for the treatment of ENKTL and may warrant translation for use in clinical trials. Funding Yang's laboratory was supported by the National Natural Science Foundation of China (Grant: 81874301), the Fundamental Research Funds for Central University (Grant: DUT22YG122) and the Key Research project of 'be Recruited and be in Command' in Liaoning Province (Personal Target Discovery for Metabolic Diseases).
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Affiliation(s)
- He Liu
- School of Bioengineering, Dalian University of TechnologyDalianChina
| | - Meisuo Liu
- School of Bioengineering, Dalian University of TechnologyDalianChina
| | - Xibao Tian
- School of Bioengineering, Dalian University of TechnologyDalianChina
| | - Haina Wang
- School of Bioengineering, Dalian University of TechnologyDalianChina
| | - Jiujiao Gao
- School of Bioengineering, Dalian University of TechnologyDalianChina
| | - Hanrui Li
- School of Bioengineering, Dalian University of TechnologyDalianChina
| | - Zhehuan Zhao
- School of Software, Dalian University of TechnologyDalianChina
| | - Yu Liu
- School of Software, Dalian University of TechnologyDalianChina
| | - Caigang Liu
- Department of Oncology, Shengjing Hospital of China Medical UniversityShenyangChina
| | - Xuan Chen
- School of Bioengineering, Dalian University of TechnologyDalianChina
- School of Software, Dalian University of TechnologyDalianChina
| | - Yongliang Yang
- School of Bioengineering, Dalian University of TechnologyDalianChina
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15
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Tachita T, Takahata T, Yamashita S, Ebina T, Kamata K, Yamagata K, Tamai Y, Sakuraba H. Newly diagnosed extranodal NK/T-cell lymphoma, nasal type, at the injected left arm after BNT162b2 mRNA COVID-19 vaccination. Int J Hematol 2023; 118:503-507. [PMID: 37093551 PMCID: PMC10124685 DOI: 10.1007/s12185-023-03607-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 04/17/2023] [Accepted: 04/18/2023] [Indexed: 04/25/2023]
Abstract
Anti-SARS-CoV-2 vaccines were developed in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the BNT162b2 mRNA vaccine is effective, adverse effects have been reported. Here, we report a case of extranodal NK/T-cell lymphoma, nasal type (ENKL), of the left arm following BNT162b2 mRNA vaccination. A 73-year-old male presented with a lump in the left arm, which was the site where he received the BNT162b2 mRNA vaccine 3 months prior. He was treated with topical corticosteroids and debridement, but the tumor progressed. Additionally, fever, night sweats, and general fatigue were observed. Laboratory findings included thrombocytopenia, elevated lactate dehydrogenase, and soluble interleukin-2 receptor levels. Skin biopsy led to a diagnosis of ENKL. The patient was treated with a 50% dose of SMILE therapy and radiotherapy, resulting in regression of the tumor. It seems that latent Epstein-Barr virus (EBV)-infected NK/T cells were reactivated by vaccination and contributed to the onset of ENKL. This is the first report of ENKL after BNT162b2 mRNA vaccination. The present case highlights the possible risk of development of malignant lymphoma, including ENKL at the injection site, after BNT162b2 COVID-19 vaccination.
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Affiliation(s)
- Takuto Tachita
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-Cho, Hirosaki, , Aomori, 036-8562, Japan.
| | - Takenori Takahata
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-Cho, Hirosaki, , Aomori, 036-8562, Japan
| | - Satoru Yamashita
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-Cho, Hirosaki, , Aomori, 036-8562, Japan
| | - Toru Ebina
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-Cho, Hirosaki, , Aomori, 036-8562, Japan
| | - Kosuke Kamata
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-Cho, Hirosaki, , Aomori, 036-8562, Japan
| | - Kazufumi Yamagata
- Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, Hirosaki, Japan
| | - Yoshiko Tamai
- Department of Transfusion and Cell Therapy Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Hirotake Sakuraba
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-Cho, Hirosaki, , Aomori, 036-8562, Japan
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16
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Dhodapkar RM, Spadaro JZ, Heng JS, Sinard JH, Lee YH, Habib LA, Pointdujour-Lim R. NK/T-cell Lymphoma With Orbital Involvement: A Case Report and Systematic Review of the Literature. Ophthalmic Plast Reconstr Surg 2023; 39:316-327. [PMID: 36692957 DOI: 10.1097/iop.0000000000002317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
PURPOSE To present the clinical course of a patient with recurrent NK/T-cell lymphoma (NKTL) involving the orbit and to review the literature on patients with NKTL involving the orbit. METHODS The PubMed database was searched for all cases of NKTL involving orbital, intraocular, or adnexal ocular structures. RESULTS Ninety-six patients were included in the final analysis. The mean age of diagnosis was 48.1 ± 16.8 years. The patients were 53/96 (55.2%) male and 43/96 (44.8%) female. Tumor location varied and included the orbit in 80/96 (83.3%), nasosinus in 56/96 (58.3%), uvea in 11/96 (11.5%), lacrimal gland in 9/96 (9.4%), lacrimal drainage system in 11/96 (11.5%), and conjunctiva in 7/96 (7.3%) cases. Management included surgical debulking in 29/96 (30.2%) cases, radiotherapy in 52/96 (54.2%) cases, and chemotherapy in 82/96 (85.4%) cases. Median survival was 6 months (95% CI: 5-9). Chemotherapy (hazard ratio = 0.80, 95% CI: 0.67-0.95, p = 0.013), radiotherapy (hazard ratio = 0.75, 95% CI: 0.64-0.87, p < 0.001), and orbital involvement being a recurrence of disease (hazard ratio = 0.79, 95% CI: 0.67-0.95, p = 0.009) were associated with improved survival. Advanced Ann Arbor stage (III-IV) at diagnosis (hazard ratio = 1.22, 95% CI: 1.08-1.38, p = 0.001), vision loss (hazard ratio = 1.18, 95% CI: 1.04-1.34, p = 0.009), proptosis (hazard ratio = 1.15, 95% CI: 1.01-1.30, p = 0.035) and periorbital swelling (hazard ratio = 1.15, 95% CI: 1.00-1.33, p = 0.048) were associated with poor survival. CONCLUSIONS NK/T-cell lymphoma involving the orbit, globe, or ocular adnexa heralds a poor prognosis where early diagnosis and therapy are critical. The use of radiotherapy and chemotherapy is associated with improved survival.
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Affiliation(s)
- Rahul M Dhodapkar
- Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut, U.S.A
| | - Jane Z Spadaro
- Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut, U.S.A
| | - Jacob S Heng
- Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut, U.S.A
| | - John H Sinard
- Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut, U.S.A
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut, U.S.A
| | - Yan Ho Lee
- Division of Otolaryngology, Department of Surgery, Yale School of Medicine, New Haven, Connecticut, U.S.A
| | - Larissa A Habib
- Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut, U.S.A
| | - Renelle Pointdujour-Lim
- Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut, U.S.A
- Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, U.S.A
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17
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Huang W, Liu X, Li L, Zhang Y, Gao Y, Gao J, Kang L. Multimodality imaging evaluation of primary testicular extranodal natural killer/T-cell lymphoma: two case reports. Front Med (Lausanne) 2023; 10:1183564. [PMID: 37324131 PMCID: PMC10267869 DOI: 10.3389/fmed.2023.1183564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 05/11/2023] [Indexed: 06/17/2023] Open
Abstract
Background Extranodal natural killer/T-cell lymphoma (ENKTCL) is a distinct pathological entity and accounts for ~10% of T-cell lymphomas. The histological features of ENKTCL include angiodestruction and coagulative necrosis and the association with EBV infection. ENKTCL is typically aggressive and mainly affects the nasal cavity and nasopharyngeal region. However, some patients can present with distant nodal or extranodal involvement such as the Waldeyer ring, gastrointestinal tract, genitourinary organs, lung, thyroid, skin, and testes. Compared to ENKTCL of nasal type, primary testicular ENKTCL is very rare and has a lower age of onset and faster clinical progression, with tumor cell dissemination occurring early in the disease. Case report Case 1: A 23-year-old man presented with 1 month of right testicular pain and swelling. Enhancement CT revealed increased density in the right testis, uneven increased enhancement, discontinuity of the local envelope, and multiple trophoblastic vessels in the arterial phase. Testicular ENKTCL was diagnosed by post-operative pathology. The patient underwent a follow-up 18F-FDG PET/CT imaging 1 month later and found elevated metabolism in the bilateral nasal, left testicular, and right inguinal lymph nodes. Unfortunately, the patient received no further treatment and died 6 months later. Case 2: A 2-year-old male child presented with an enlarged right testicle, MRI showed a mass in the right epididymis and testicular area, which showed low signal on T1WI, high signal on T2WI and DWI, and low signal on ADC. Meanwhile, CT showed soft tissue in the lower lobe of the left lung and multiple high-density nodules of varying sizes in both lungs. Based on the post-operative pathology, the lesion was diagnosed with primary testicular ENKTCL. The pulmonary lesion was diagnosed as hemophagocytic lymphohistiocytosis associated with EBV infection. The child was given SMILE chemotherapy, but pancreatitis was induced during chemotherapy, then he died 5 months later after chemotherapy. Conclusion Primary testicular ENKTCL is very rare in clinical practice, typically presenting as a painful testicular mass, which can mimic inflammatory lesions and cause diagnostic challenges. 18F-FDG PET/CT plays pivotal roles in the diagnosis, staging, evaluation of treatment outcomes and prognosis evaluation in patients with testicular ENKTCL, and it is helpful to assist clinical practice to better formulate individualized treatment plans.
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Affiliation(s)
- Wenpeng Huang
- Department of Nuclear Medicine, Peking University First Hospital, Beijing, China
| | - Xiaonan Liu
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Liming Li
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yongbai Zhang
- Department of Nuclear Medicine, Peking University First Hospital, Beijing, China
| | - Yuan Gao
- Department of Nuclear Medicine, Peking University First Hospital, Beijing, China
| | - Jianbo Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Lei Kang
- Department of Nuclear Medicine, Peking University First Hospital, Beijing, China
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18
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Aggressive Cutaneous Lymphomas and Their Mimics. Surg Pathol Clin 2023; 16:361-383. [PMID: 37149363 DOI: 10.1016/j.path.2023.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
Abstract
Cutaneous lymphomas encompass a heterogeneous group of neoplasms with a wide spectrum of clinical presentations, histopathologic features, and prognosis. Because there are overlapping pathologic features among indolent and aggressive forms and with systemic lymphomas that involve the skin, clinicopathologic correlation is essential. Herein, the clinical and histopathologic features of aggressive cutaneous B- and T-cell lymphomas are reviewed. Indolent cutaneous lymphomas/lymphoproliferative disorders, systemic lymphomas, and reactive processes that may mimic these entities are also discussed. This article highlights distinctive clinical and histopathologic features, increases awareness of rare entities, and presents new and evolving developments in the field.
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19
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Tian XP, Zhang YC, Lin NJ, Wang L, Li ZH, Guo HG, Ma SY, An MJ, Yang J, Hong YH, Wang XH, Zhou H, Li YJ, Rao HL, Li M, Hu SX, Lin TY, Li ZM, Huang H, Liang Y, Xia ZJ, Lv Y, Liu YY, Duan ZH, Chen QY, Wang JN, Cai J, Xie Y, Ong CK, Liu F, Liu YY, Yan Z, Huang L, Tao R, Li WY, Huang HQ, Cai QQ. Diagnostic performance and prognostic value of circulating tumor DNA methylation marker in extranodal natural killer/T cell lymphoma. Cell Rep Med 2023; 4:100859. [PMID: 36812892 PMCID: PMC9975248 DOI: 10.1016/j.xcrm.2022.100859] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 07/12/2022] [Accepted: 11/18/2022] [Indexed: 02/23/2023]
Abstract
Circulating tumor DNA (ctDNA) carries tumor-specific genetic and epigenetic variations. To identify extranodal natural killer/T cell lymphoma (ENKTL)-specific methylation markers and establish a diagnostic and prognosis prediction model for ENKTL, we describe the ENKTL-specific ctDNA methylation patterns by analyzing the methylation profiles of ENKTL plasma samples. We construct a diagnostic prediction model based on ctDNA methylation markers with both high specificity and sensitivity and close relevance to tumor staging and therapeutic response. Subsequently, we built a prognostic prediction model showing excellent performance, and its predictive accuracy is significantly better than the Ann Arbor staging and prognostic index of natural killer lymphoma (PINK) risk system. Notably, we further establish a PINK-C risk grading system to select individualized treatment for patients with different prognostic risks. In conclusion, these results suggest that ctDNA methylation markers are of great value in diagnosis, monitoring, and prognosis, which might have implications for clinical decision-making of patients with ENKTL.
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Affiliation(s)
- Xiao-Peng Tian
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Yu-Chen Zhang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Ning-Jing Lin
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Liang Wang
- Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
| | - Zhi-Hua Li
- Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, P. R. China
| | - Han-Guo Guo
- Division of Lymphoma, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Shu-Yun Ma
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Ming-Jie An
- Department of Urology, Sun Yat-sen Memorial Hospital, Guangzhou, P.R. China
| | - Jing Yang
- Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
| | - Yu-Heng Hong
- Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P.R. China
| | - Xian-Huo Wang
- Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P.R. China
| | - Hui Zhou
- Department of Lymphoma and Hematology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P.R. China
| | - Ya-Jun Li
- Department of Lymphoma and Hematology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P.R. China
| | - Hui-Lan Rao
- Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Mei Li
- Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Shao-Xuan Hu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Tong-Yu Lin
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Zhi-Ming Li
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - He Huang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Yang Liang
- Department of Hematology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Zhong-Jun Xia
- Department of Hematology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Yue Lv
- Department of Hematology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Yu-Ying Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Zhao-Hui Duan
- Department of Clinical Laboratory, Sun Yat-sen Memorial Hospital, Guangzhou, P.R. China
| | - Qing-Yu Chen
- Department of Medical Examination Center, Sun Yat-sen Memorial Hospital, Guangzhou, P.R. China
| | - Jin-Ni Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Jun Cai
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Ying Xie
- Guangdong Provincial Academy of Chinese Medical Sciences, State Key Laboratory of Dampness Syndrome of Chinese Medicine, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, P.R. China
| | - Choon-Kiat Ong
- Lymphoma Genomic Translational Research Laboratory, Division of Cellular and Molecular Research, National Cancer Centre Singapore, 11 Hospital Drive, 169610 Singapore, Singapore
| | - Fang Liu
- Department of Pathology, The First People's Hospital of Foshan, Foshan, P.R. China
| | - Yan-Yan Liu
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou 450008, P.R. China
| | - Zheng Yan
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou 450008, P.R. China
| | - Liang Huang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Rong Tao
- Department of Lymphoma, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
| | - Wen-Yu Li
- Department of Urology, Sun Yat-sen Memorial Hospital, Guangzhou, P.R. China.
| | - Hui-Qiang Huang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
| | - Qing-Qing Cai
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
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20
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Elshanbary AA, Zilai AH, Ishqair A, Matar SG, Nourelden AZ, Hafez AH, Altyar AE, Albadrani GM, Zaazouee MS. Demographic and treatment risk factors of cancer-specific mortality among children and adolescent leukemia patients: a population-based study. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:19182-19193. [PMID: 36220963 DOI: 10.1007/s11356-022-23425-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 09/29/2022] [Indexed: 06/16/2023]
Abstract
Leukemia is the 15th most commonly diagnosed cancer and the 11th leading cause of cancer mortality. The high mortality rate of leukemia could be attributed to numerous factors. Therefore, we aimed to identify the demographic and treatment risk factors influencing mortality among patients diagnosed with leukemia. Patients' data from 1975 to 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. We used the Person's chi-square test to examine the associations among the categorical variables. Kaplan-Meier and Cox regression were applied for univariate and multivariate analyses. Standardized mortality ratios were utilized to compare the mortality rates of leukemia patients and the general US population. We carried out the statistical analysis using SPSS software. A total of 18,880 patients with leukemia were studied. The leukemia incidence was increased in children than in adolescents. Acute lymphoid leukemia (ALL) was the most common type diagnosed among children and adolescents: 10,331 and 4112 patients, respectively. All mortality ratios were significantly higher in leukemia patients compared to the US population. The risk of mortality among leukemia patients was higher among adolescents, females, Black, urban areas with a 20,000 population, and patients not receiving chemotherapy. In contrast, the mortality risk was decreased in patients with higher family incomes, those not treated with radiation, and diagnosed from 2000 to 2016. In conclusion, Leukemia's incidence increases with time. Adolescents, males, Black, in some urban areas, and patients who have not received chemotherapy had the highest mortality risk among leukemia patients.
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Affiliation(s)
| | - Ayat Hassan Zilai
- Department of Pediatrics, King Salman Hospital, Riyadh, Saudi Arabia
| | - Anas Ishqair
- Faculty of Medicine, The Hashemite University, Zarqa, Jordan
| | | | | | | | - Ahmed E Altyar
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Ghadeer M Albadrani
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia
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21
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Muacevic A, Adler JR. Long-Term Outcomes of Definitive Chemoradiotherapy for Early-Stage Extranodal Natural Killer/T-cell Lymphoma, Nasal Type: A Retrospective Analysis From a Single Center. Cureus 2023; 15:e34348. [PMID: 36865952 PMCID: PMC9974215 DOI: 10.7759/cureus.34348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2023] [Indexed: 01/30/2023] Open
Abstract
Background Nasal extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is a rare type of lymphoma with characteristic histological features. Although radiotherapy can achieve a high response rate, long-term efficacy and safety are yet to be established. Methodology Using electronic health records, we identified relevant patients treated at our hospital from August 2005 to August 2015. We enrolled patients with pathologically confirmed ENKTL treated with curative intent radiotherapy. Results We included 13 patients who underwent definitive radiotherapy in the analysis, comprising 11 males and 2 females and a median age of 53 years (range: 28-73). The median follow-up period was 113.4 months. The overall survival at 5 and 10 years was 92.3% (95% confidence interval [CI]: 57-99 %) and 68.4% (95% CI: 29-89 %), respectively. The most common radiation-related late-term toxicity was sinus disorder (Grade 1-2) in 11 patients (85%). Radiation-related grade 3 to 5 toxicities were not observed. Conclusion The present retrospective study elucidated the long-term safety and effectiveness of curative intent radiotherapy in patients with localized ENKTL.
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Affiliation(s)
| | - John R Adler
- Radiology, University of Tokyo Hospital, Tokyo, JPN
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22
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Bitner BF, Htun NN, Wang BY, Brem EA, Kuan EC. Sinonasal lymphoma: A primer for otolaryngologists. Laryngoscope Investig Otolaryngol 2022; 7:1712-1724. [PMID: 36544932 PMCID: PMC9764779 DOI: 10.1002/lio2.941] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/28/2022] [Accepted: 09/20/2022] [Indexed: 12/24/2022] Open
Abstract
Objective Sinonasal lymphomas are a rare entity that commonly present with nonspecific sinonasal symptoms and are often recognized immediately. Through this review, we aim to summarize important principles in diagnosis and treatment of sinonasal lymphomas, with the goal of disseminating the current knowledge of this under-recognized malignancy to otolaryngologists. Methods Systemic review using PRISMA guidelines of foundational scholarly articles, guidelines, and trials were reviewed focusing on clinical characteristics of key sinonasal lymphoma subtypes, along with available treatments in the otolaryngology, medical oncology, and radiation oncology literature. Results Sinonasal lymphoma are derived from clonal proliferation of lymphocytes at various stages of differentiation, of which diffuse large B-cell lymphoma (DLBCL) and extranodal natural killer/T-cell lymphoma (ENKTL) are the most common. Diagnosis and staging require biopsy with immunohistochemistry in conjunction with imaging and laboratory studies. Treatment is ever evolving and currently includes multi-agent chemotherapy and/or radiation therapy. Conclusion Otolaryngologists may be the first to recognize sinonasal lymphoma, which requires a comprehensive workup and a multidisciplinary team for treatment. Symptoms are nonspecific and similar to many sinonasal pathologies, and it is crucial for otolaryngologists to keep a broad differential. Level of Evidence 5.
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Affiliation(s)
- Benjamin F. Bitner
- Department of Otolaryngology – Head and Neck SurgeryUniversity of California Irvine Medical CenterOrangeCaliforniaUSA
| | - Nyein Nyein Htun
- Department of Pathology and Laboratory MedicineUniversity of California Irvine Medical CenterOrangeCaliforniaUSA
| | - Beverly Y. Wang
- Department of Pathology and Laboratory MedicineUniversity of California Irvine Medical CenterOrangeCaliforniaUSA
| | - Elizabeth A. Brem
- Department of Medicine, Division of Hematology and OncologyUniversity of California Irvine Medical CenterOrangeCaliforniaUSA
| | - Edward C. Kuan
- Department of Otolaryngology – Head and Neck SurgeryUniversity of California Irvine Medical CenterOrangeCaliforniaUSA
- Department of Neurological SurgeryUniversity of California Irvine Medical CenterOrangeCaliforniaUSA
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23
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Wang H, Fu BB, Wuxiao ZJ, Li YJ, Huang L, Ma J, Zhai ZM, Guo J, Wu YB, Xu ZS, Feng J, Zhou SS, Chen TT, Chen XG, Li GW, Liu TZ, Huang HB, Zheng RH, Li YH, Tao HF, Zi FM, Wu F, Wang J, Zeng H, Fu CB, Gale RP, Xia ZJ, Liang Y. A prognostic survival nomogram for persons with extra-nodal natural killer-/T-cell lymphoma. Leukemia 2022; 36:2724-2728. [PMID: 35970944 DOI: 10.1038/s41375-022-01679-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 07/29/2022] [Accepted: 08/02/2022] [Indexed: 02/05/2023]
Affiliation(s)
- Hua Wang
- Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, PR China
| | - Bi-Bo Fu
- Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, PR China
| | - Zhi-Jun Wuxiao
- Department of Hematology, Lymphoma and Myeloma Center, HMC Cancer Institute, The First Affiliated Hospital of Hainan Medical University, Haikou City, Hainan, PR China
| | - Ya-Jun Li
- Department of Lymphoma and Hematology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China
| | - Li Huang
- Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China
| | - Jie Ma
- Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Zhi-Min Zhai
- Department of Hematology, The Second Hospital of Anhui Medical University, Hefei, Anhui, PR China
| | - Jing Guo
- Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China
| | - Yuan-Bin Wu
- Department of Hematology, Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, PR China
| | - Zhen-Shu Xu
- Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, PR China
| | - Jia Feng
- Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, PR China
| | - Sheng-Sheng Zhou
- Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Ting-Ting Chen
- Department of Hematology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University), Shenzhen, PR China
| | - Xing-Gui Chen
- Cancer Center, Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong, PR China
| | - Guo-Wei Li
- Department of Hematology, Huizhou Municipal Central Hospital, Huizhou, Guangdong, PR China
| | - Ting-Zhi Liu
- Department of Medical Hematology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangdong gastrointestinal hospital, Guangzhou, Guangdong, PR China
| | - Hai-Bin Huang
- Department of Hematology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, PR China
| | - Run-Hui Zheng
- Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, PR China
| | - Yong-Hua Li
- Department of Hematology, General Hospital of Southern Theater Command, PLA, Guangzhou, Guangdong, PR China
| | - Hong-Fang Tao
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, PR China
| | - Fu-Ming Zi
- Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
| | - Fan Wu
- Department of Hematology, The Second Hospital of Anhui Medical University, Hefei, Anhui, PR China
| | - Juan Wang
- Department of Hematology, The Second Hospital of Anhui Medical University, Hefei, Anhui, PR China
| | - Hui Zeng
- Department of Hematology, The First Affiliated Hospital of Jinan university, Guangzhou, Guangdong, PR China
| | - Cai-Bo Fu
- Department of Hematology, Lymphoma and Myeloma Center, HMC Cancer Institute, The First Affiliated Hospital of Hainan Medical University, Haikou City, Hainan, PR China
| | - Robert Peter Gale
- Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, PR China
- Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK
| | - Zhong-Jun Xia
- Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, PR China
| | - Yang Liang
- Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, PR China
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24
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Qiu C, Du G. Loss of
LEF
‐1 expression as a diagnostic indicator for extranodal
NK
/T‐cell lymphoma: An immunohistochemical study of 88 cases. Eur J Haematol 2022; 109:513-518. [PMID: 35871391 DOI: 10.1111/ejh.13836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 07/02/2022] [Accepted: 07/05/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Cen Qiu
- Department of Pathology, the Ninth People's Hospital Shanghai Jiaotong University School of Medicine China
| | - Guangye Du
- Department of Pathology, the Ninth People's Hospital Shanghai Jiaotong University School of Medicine China
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25
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Hue SSS, Ng SB, Wang S, Tan SY. Cellular Origins and Pathogenesis of Gastrointestinal NK- and T-Cell Lymphoproliferative Disorders. Cancers (Basel) 2022; 14:2483. [PMID: 35626087 PMCID: PMC9139583 DOI: 10.3390/cancers14102483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/08/2022] [Accepted: 05/13/2022] [Indexed: 11/25/2022] Open
Abstract
The intestinal immune system, which must ensure appropriate immune responses to both pathogens and commensal microflora, comprises innate lymphoid cells and various T-cell subsets, including intra-epithelial lymphocytes (IELs). An example of innate lymphoid cells is natural killer cells, which may be classified into tissue-resident, CD56bright NK-cells that serve a regulatory function and more mature, circulating CD56dim NK-cells with effector cytolytic properties. CD56bright NK-cells in the gastrointestinal tract give rise to indolent NK-cell enteropathy and lymphomatoid gastropathy, as well as the aggressive extranodal NK/T cell lymphoma, the latter following activation by EBV infection and neoplastic transformation. Conventional CD4+ TCRαβ+ and CD8αβ+ TCRαβ+ T-cells are located in the lamina propria and the intraepithelial compartment of intestinal mucosa as type 'a' IELs. They are the putative cells of origin for CD4+ and CD8+ indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and intestinal T-cell lymphoma, NOS. In addition to such conventional T-cells, there are non-conventional T-cells in the intra-epithelial compartment that express CD8αα and innate lymphoid cells that lack TCRs. The central feature of type 'b' IELs is the expression of CD8αα homodimers, seen in monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), which primarily arises from both CD8αα+ TCRαβ+ and CD8αα+ TCRγδ+ IELs. EATL is the other epitheliotropic T-cell lymphoma in the GI tract, a subset of which arises from the expansion and reprograming of intracytoplasmic CD3+ innate lymphoid cells, driven by IL15 and mutations of the JAK-STAT pathway.
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Affiliation(s)
- Susan Swee-Shan Hue
- Department of Pathology, National University Hospital, Singapore 119074, Singapore; (S.S.-S.H.); (S.W.)
| | - Siok-Bian Ng
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore;
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
| | - Shi Wang
- Department of Pathology, National University Hospital, Singapore 119074, Singapore; (S.S.-S.H.); (S.W.)
| | - Soo-Yong Tan
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore;
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26
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Qian WS, Shen L, Wulipan F, Wu M, Ma JX, Chen PP, Xu Y, Xie YH. [Clinical characteristics and prognosis of patients with aggressive NK cell leukemia]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2022; 43:424-426. [PMID: 35680601 PMCID: PMC9250961 DOI: 10.3760/cma.j.issn.0253-2727.2022.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- W S Qian
- Department of Hematology, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - L Shen
- Department of Hematology, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - Fulati Wulipan
- Department of Hematology, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - M Wu
- Department of Hematology, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - J X Ma
- Department of Hematology, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - P P Chen
- Department of Hematology, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - Y Xu
- Department of Hematology, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - Y H Xie
- Department of Hematology, Huadong Hospital, Fudan University, Shanghai 200040, China
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27
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Bennani NN, Tun AM, Carson KR, Geiger JL, Maeda LS, Savage KJ, Rose J, Pinter-Brown L, Lunning MA, Abramson JS, Bartlett NL, Vose JM, Evens AM, Smith SM, Horwitz SM, Ansell SM, Advani RH. Characteristics and Outcome of Extranodal NK/T-cell Lymphoma in North America: A Retrospective Multi-Institutional Experience. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2022; 22:e300-e309. [PMID: 34848181 DOI: 10.1016/j.clml.2021.10.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/18/2021] [Accepted: 10/28/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Extranodal natural killer/T-cell lymphoma (ENKTL) is rare and clinical data from non-Asian countries are lacking. It is unclear whether outcomes and disease natural history is similar to reported Asian series. We assessed characteristics and outcomes of patients with ENKTL from major North American centers. PATIENTS AND METHODS We retrospectively identified patients with newly-diagnosed CD56 + ENKTL and studied disease characteristics and clinical outcomes. RESULTS One hundred and twenty-one patients with ENKTL diagnosed between June 1990 and November 2012 were identified. Eighty-three patients (69%) had stage I/II disease and were treated with combined modality therapy (CMT) (n = 53), chemotherapy alone (CT) (n = 14) or radiotherapy alone (RT) (n = 16). Thirty-eight patients (31%) had stage III/IV disease and were treated with CMT (n = 12), CT (n = 23), or RT (n = 3). The median follow-up for the entire cohort was 51 months. Patients with stage I/II disease, compared to those with stage III/IV disease, had superior 2-year progression free survival (PFS) 43% vs 19% (P = .03) and overall survival (OS) 59% vs. 29% (P= .004). Outcomes were similar for stage I/II patients who received CMT vs. RT alone with 2-year PFS (53% vs. 47%; P= .91) and OS (67% vs. 67%; P= .58). No significant differences in outcomes were noted based on race/ethnicity. CONCLUSIONS This series represents a large experience of ENKTL treated at several major North American academic centers. Our data are consistent with Asian studies: (1) majority of patients present with early-stage disease; (2) overall poor outcome regardless of race/ethnicity; (3) CMT likely yields favorable outcomes for suitable candidates with early-stage disease.
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Affiliation(s)
| | - Aung M Tun
- Division of Hematology, Mayo Clinic, Rochester, MN; Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center, Kansas City, KS
| | - Kenneth R Carson
- Research Service, St Louis Veterans Affairs Medical Center, St. Louis, MO; Division of Oncology, Washington University School of Medicine, St. Louis, MO
| | | | | | - Kerry J Savage
- Centre for Lymphoid Cancer and Department of Medical Oncology, BC Cancer, Vancouver, BC
| | - Jim Rose
- Centre for Lymphoid Cancer and Department of Medical Oncology, BC Cancer, Vancouver, BC
| | | | - Matthew A Lunning
- Divisions of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE
| | - Jeremy S Abramson
- Divisions of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, MA
| | - Nancy L Bartlett
- Division of Oncology, Washington University School of Medicine, St. Louis, MO
| | - Julie M Vose
- Divisions of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE
| | | | - Sonali M Smith
- Divisions of Hematology/Oncology, University of Chicago, Chicago, IL
| | - Steven M Horwitz
- Division of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY
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28
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Liu C, Ding H, Zhu Q, Liu P, Zhu Y, Wang L, Ma Y, Zhang W, Tian S, Zhang X, Jin L, Liu L, Li Z, Hao S, Tao R. Induction with MEDA regimen and consolidation with Auto-HSCT for stage IV NKTCL patients: a prospective multicenter study. Int J Cancer 2022; 151:752-763. [PMID: 35489026 DOI: 10.1002/ijc.34055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 03/31/2022] [Accepted: 04/13/2022] [Indexed: 11/11/2022]
Abstract
Optimal treatment strategies for natural killer/T-cell lymphoma (NKTCL) patients with stage IV disease have not been well defined. In this prospective phase 2 study, we evaluated the treatment using MEDA (methotrexate, etoposide, dexamethasone, and pegaspargase) as induction chemotherapy and autologous hematopoietic stem cell transplantation (Auto-HSCT) for consolidation. Patients with stage IV disease without prior L-asparaginase-based chemotherapy were eligible. Four cycles of MEDA were administered as induction treatment. Patients with complete response (CR, necessary to have complete metabolic remission of PET/CT, negative plasma EBV-DNA, and negative EBER staining of bone marrow biopsy tissue) were consolidated by Auto-HSCT. A total of 53 patients were enrolled. The overall response (OR) rate and CR rate after four cycles of MEDA chemotherapy were 75.5% and 56.6%, respectively. Among them, 25 patients underwent Auto-HSCT. The 4-year overall survival (OS) rate and progression-free survival (PFS) rate were 58.0% (95%CI, 43.4% to 70.0%) and 43.4% (95% CI, 29.9% to 56.1%), respectively. Patients who underwent Auto-HSCT had a 4-year OS rate of 92.0% (95% CI, 71.6% to 97.9%) and a 4-year PFS rate of 80.0% (95% CI, 58.4% to 91.1%). Grade 3/4 neutropenia and thrombocytopenia occurred in 28.3% and 17.0% of the patients, respectively. MEDA chemotherapy is an effective induction regimen with reduced grade 3/4 hematological toxicities for stage IV NKTCL. Consolidation with Auto-HSCT can be considered as a potential approach to improve the long-term survival of CR patients after induction treatment. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Chuanxu Liu
- Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hao Ding
- Department of Radiation Oncology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, China
| | - Qi Zhu
- Department of Hematology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Peng Liu
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yang Zhu
- Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lifeng Wang
- Department of Pathology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yujie Ma
- Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenhao Zhang
- Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shu Tian
- Department of Radiation Oncology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, China
| | - Xiaoyan Zhang
- Department of Hematology, Xin Jiang People's Hospital, Xin Jiang, China
| | - Lina Jin
- Department of Hematology, Dongfang Hospital, Tongji University, Shanghai, China
| | - Ligen Liu
- Department of hematology, Tongren Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhichao Li
- Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Siguo Hao
- Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rong Tao
- Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Shafiee A, Shamsi S, Kohandel Gargari O, Beiky M, Allahkarami MM, Miyanaji AB, Aghajanian S, Mozhgani SH. EBV associated T- and NK-cell lymphoproliferative diseases: A comprehensive overview of clinical manifestations and novel therapeutic insights. Rev Med Virol 2022; 32:e2328. [PMID: 35122349 DOI: 10.1002/rmv.2328] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 12/27/2021] [Accepted: 01/13/2022] [Indexed: 11/09/2022]
Abstract
EBV is a ubiquitous virus that infects nearly all people around the world. Most infected people are asymptomatic and do not show serious sequelae, while others may develop Epstein-Barr virus (EBV)-positive T and NK-cell lymphoproliferations characterised by EBV-infected T or NK cells. These disorders are more common in Asian and Latin American people, suggesting genetic predisposition as a contributing factor. The revised WHO classification classifies the lymphoproliferative diseases as: extranodal NK/T-cell lymphoma nasal type (ENKTL), aggressive NK-cell leukemia (ANKL), primary EBV-positive nodal T or NK cell lymphoma (NNKTL), systemic EBV-positive T-cell lymphoproliferative disease of childhood (STCLC), systemic chronic active EBV infection (sys CAEBV), hydroa-vacciniforme (HV) and severe mosquito bite allergy (SMBA). Recent advances in the molecular pathogenesis of these diseases have led to the development of new therapeutic strategies. Due to the infrequency of the diseases and broad clinicopathological overlap, the diagnosis and classification are challenging for both clinicians and pathologists. In this article, we aim to review the recent pathological findings which can be helpful for designing new drugs, clinical presentations and differential diagnoses, and suggested therapeutic interventions to provide a better understanding of these rare disorders.
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Affiliation(s)
- Arman Shafiee
- Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
| | - Sahel Shamsi
- Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
| | | | - Maryam Beiky
- Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
| | | | | | - Sepehr Aghajanian
- Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
| | - Sayed-Hamidreza Mozhgani
- Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.,Non-communicable Disease Research Center, Alborz University of Medical Sciences, Karaj, Iran
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30
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The Pathologic and Genetic Characteristics of Extranodal NK/T-Cell Lymphoma. Life (Basel) 2022; 12:life12010073. [PMID: 35054466 PMCID: PMC8781285 DOI: 10.3390/life12010073] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 01/01/2022] [Accepted: 01/03/2022] [Indexed: 12/14/2022] Open
Abstract
Extranodal NK/T-cell lymphoma is a neoplasm of NK cells or cytotoxic T cells presenting in extranodal sites, most often in the nasal cavity. The typical immunophenotypes are cCD3+, sCD3-, CD4-, CD5-, CD8-, CD16-, and CD56+ with the expression of cytotoxic molecules. Tumor subsets express NK cell receptors, CD95/CD95L, CD30, MYC, and PDL1. Virtually all the tumor cells harbor the EBV genome, which plays a key role in lymphomagenesis as an epigenetic driver. EBV-encoded oncoproteins modulate the host-cell epigenetic machinery, reprogramming the viral and host epigenomes using host epigenetic modifiers. NGS analysis revealed the mutational landscape of ENKTL, predominantly involving the JAK-STAT pathway, epigenetic modifications, the RNA helicase family, the RAS/MAP kinase pathway, and tumor suppressors, which indicate an important role of these pathways and this group of genes in the lymphomagenesis of ENKTL. Recently, three molecular subtypes were proposed, the tumor-suppressor/immune-modulator (TSIM), MGA-BRDT (MB), and HDAC9-EP300-ARID1A (HEA) subtypes, and they are well-correlated with the cell of origin, EBV pattern, genomic alterations, and clinical outcomes. A future investigation into the function and interaction of discovered genes would be very helpful for better understanding the molecular pathogenesis of ENKTL and establishing better treatment strategies.
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31
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Yang R, Ai Y, Liu C, Lu X. Aggressive Natural Killer Cell Leukemia in an Adolescent Patient: A Case Report and Literature Review. Front Pediatr 2022; 10:829927. [PMID: 35676895 PMCID: PMC9168658 DOI: 10.3389/fped.2022.829927] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 03/28/2022] [Indexed: 12/16/2022] Open
Abstract
Aggressive natural killer cell leukemia (ANKL) is a rare malignant tumor, especially uncommon in children. ANKL has very aggressive clinical course and bad prognosis and is usually caused by Epstein-Barr virus infection. ANKL often has clinical manifestations of hemophagocytic lymphohistiocytosis (HLH) and can be easily treated as HLH, which might complicate this aggressive disease. Here we report an ANKL in adolescent whose clinical presentation was highly aggressive and response to L-asparaginase containing chemotherapy was very bad. Early-onset Flow cytometry of peripheral blood and bone marrow help make the diagnosis.
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Affiliation(s)
- Rong Yang
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.,Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Yuan Ai
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.,Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Chuan Liu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.,Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Xiaoxi Lu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.,Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
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32
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Peng XH, Zhang LS, Li LJ, Guo XJ, Liu Y. Aggressive natural killer cell leukemia with skin manifestation associated with hemophagocytic lymphohistiocytosis: A case report. World J Clin Cases 2021; 9:10708-10714. [PMID: 35005005 PMCID: PMC8686140 DOI: 10.12998/wjcc.v9.i34.10708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 07/08/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Aggressive natural killer cell leukemia (ANKL) is a rare natural killer cell neoplasm characterized by systemic infiltration of Epstein–Barr virus and rapidly progressive clinical course. ANKL can be accompanied with hemophagocytic lymphohistiocytosis (HLH). Here, we report a case of ANKL with rare skin lesions as an earlier manifestation, accompanied with HLH, and review the literature in terms of etiology, clinical manifestation, diagnosis and treatment.
CASE SUMMARY A 30-year-old woman from Northwest China presented with the clinical characteristics of jaundice, fever, erythema, splenomegaly, progressive hemocytopenia, liver failure, quantities of abnormal cells in bone marrow, and associated HLH. The immunophenotypes of abnormal cells were positive for CD2, cCD3, CD7, CD56, CD38 and negative for sCD3, CD8 and CD117. The diagnosis of ANKL complicated with HLH was confirmed. Following the initial diagnosis and supplementary treatment, the patient received chemotherapy with VDLP regimen (vincristine, daunorubicin, L-asparaginase and prednisone). However, the patient had severe adverse reactions and complication such as severe hematochezia, neutropenia, and multiple organ dysfunction syndrome, and died a few days later.
CONCLUSION This is the first reported case of ANKL with rare skin lesions as an earlier manifestation and associated with HLH.
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Affiliation(s)
- Xiao-Huan Peng
- Department of Hematology, Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Lian-Sheng Zhang
- Department of Hematology, Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Li-Juan Li
- Department of Hematology, Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Xiao-Jia Guo
- Department of Hematology, Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Yang Liu
- Department of Hematology, Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
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33
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Bennani NN, Tun AM, Carson KR, Geiger JL, Maeda LS, Savage KJ, Rose J, Pinter-Brown L, Lunning MA, Abramson JS, Bartlett NL, Vose JM, Evens AM, Smith SM, Horwitz SM, Ansell SM, Advani RH. Characteristics and Outcome of Extranodal NK/T-Cell Lymphoma in North America: A Retrospective Multi-Institutional Experience. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2021; 22:e250-e260. [PMID: 34794912 DOI: 10.1016/j.clml.2021.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 10/09/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Extranodal natural killer/T-cell lymphoma (ENKTL) is rare and clinicaldata from non-Asian countries are lacking. It is unclear whether outcomes and diseasenatural history is similar to reported Asian series. We assessed characteristics and outcomes of patients with ENKTL from major North American centers. PATIENTS AND METHODS We retrospectively identified patients with newly-diagnosedCD56 + ENKTL and studied disease characteristics and clinical outcomes. RESULTS 121 patients with ENKTL diagnosed between June 1990 and November 2012 were identified. Eighty-three patients (69%) had stage I/II disease and were treatedwith combined modality therapy (CMT) (n=53), chemotherapy alone (CT) (n=14) orradiotherapy alone (RT) (n=16). Thirty-eight patients (31%) had stage III/IV diseaseand were treated with CMT (n=12), CT (n=23), or RT (n=3). The median follow-up forthe entire cohort was 51 months. Patients with stage I/II disease, compared to thosewith stage III/IV disease, had superior 2-year progression free survival (PFS) 43% vs19% (p=0.03) and overall survival (OS) 59% vs 29% (p=0.004). Outcomes were similarfor stage I/II patients who received CMT vs RT alone with 2-year PFS (53% vs 47%;p=0.91) and OS (67% vs 67%; p=0.58). No significant differences in outcomes werenoted based on race/ethnicity. CONCLUSIONS This series represents a large experience of ENKTL treated at several major North American academic centers. OUR DATA ARE CONSISTENT WITH ASIAN STUDIES 1) majority of patients present with early-stage disease; 2) overall poor outcome regardless of race/ethnicity; 3) CMT likely yields favorable outcomes for suitable candidates with early-stage disease.
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Affiliation(s)
| | - Aung M Tun
- Division of Hematology, Mayo Clinic, Rochester, MN; Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center, Kansas City, KS
| | - Kenneth R Carson
- Research Service, St Louis Veterans Affairs Medical Center, St Louis, MO; Division of Oncology, Washington University School of Medicine, St. Louis, MO
| | | | - Lauren S Maeda
- Division of Oncology, Stanford Cancer Institute, Stanford, CA
| | - Kerry J Savage
- Department of Medical Oncology, Centre for Lymphoid Cancer, Vancouver, BC, Canada
| | - Jim Rose
- Department of Medical Oncology, Centre for Lymphoid Cancer, Vancouver, BC, Canada
| | | | - Matthew A Lunning
- Divisions of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE
| | - Jeremy S Abramson
- Divisions of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, MA
| | - Nancy L Bartlett
- Division of Oncology, Washington University School of Medicine, St. Louis, MO
| | - Julie M Vose
- Divisions of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE
| | | | - Sonali M Smith
- Divisions of Hematology/Oncology, University of Chicago, Chicago, IL
| | - Steven M Horwitz
- Division of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY
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Tvedten E, Richardson J, Motaparthi K. What Effect Does Epstein-Barr Virus Have on Extranodal Natural Killer/T-Cell Lymphoma Prognosis? A Review of 153 Reported Cases. Cureus 2021; 13:e17987. [PMID: 34540511 PMCID: PMC8445857 DOI: 10.7759/cureus.17987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/15/2021] [Indexed: 11/09/2022] Open
Abstract
The primary aim of this review is to identify the relationship between Epstein-Barr virus (EBV) and prognosis in extranodal natural killer/T-cell lymphoma (ENKTL). Additionally, a literature review of ENKTL was carried out. The investigators designed and implemented a 21-year literature review using the online databases PubMed and Google Scholar. The total number of cases analyzed was 153 (64 case reports; one comparative study; one systematic review). Information related to ENKTL from July 1999 to February 2021 was included in the study. Study variables included: patient demographics, tumor classification, screening modalities, tumor characteristics, symptomatology, treatment, and prognosis. The average age at diagnosis was 50.9 years (range: 4-90 years). Patients of Asian ethnicity were most commonly affected, and there was a 1.6:1 male to female ratio. ENKTL was most frequently detected in the head and neck region, and 53.1% of cases metastasized. Of all head and neck cases, the nose was the most affected location. Immunohistochemistry positivity included: EBV (32.0%), CD2 (96.6%), CD3ϵ (81.7%), CD43 (91.7%), CD56 (86.4%), Granzyme (97.1%), Perforin (90.9%), TIA-1 (97.8%), p53 (33.3%). The most frequently employed single treatment modality was chemotherapy alone, and 34.2% of patients expired within five years of diagnosis. The average follow-up period was 16.51 months (range: 0.25-66 months). EBV was significantly associated with metastatic ENKTL (χ2 = 4.36; CV = 3.84; p = 0.037). We found no association between EBV and ENKTL prognosis (χ2 = 17.2; CV = 21.0; p = 0.14).
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Affiliation(s)
- Erika Tvedten
- Department of Dermatology, Michigan State University, Detroit, USA
| | | | - Kiran Motaparthi
- Department of Dermatology, University of Florida, Gainesville, USA
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35
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Extranodal NK/T-Cell Lymphoma, Nasal Type: Genetic, Biologic, and Clinical Aspects with a Central Focus on Epstein-Barr Virus Relation. Microorganisms 2021; 9:microorganisms9071381. [PMID: 34202088 PMCID: PMC8304202 DOI: 10.3390/microorganisms9071381] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Accepted: 06/21/2021] [Indexed: 12/18/2022] Open
Abstract
Extranodal NK/T-Cell Lymphoma, nasal type (ENKTL-NT) has some salient aspects. The lymphoma is commonly seen in Eastern Asia, has progressive necrotic lesions in the nasal cavity, makes midfacial destructive lesions, and shows poor prognosis. The lymphoma cell is originated from either NK- or γδ T-cells, which express CD56. Since the authors first demonstrated the existence of Epstein–Barr virus (EBV) DNA and EBV oncogenic proteins in lymphoma cells, ENKTL-NT has been recognized as an EBV-associated malignancy. Because the angiocentric and polymorphous lymphoma cells are mixed with inflammatory cells on a necrotic background, the diagnosis of ENKTL-NT requires CD56 immunostaining and EBER in situ hybridization. In addition, serum the EBV DNA level is useful for the diagnosis and monitoring of ENKTL-NT. Although ENKTL-NT is refractory lymphoma, the prognosis is improved by the development of therapies such as concomitant chemoradiotherapy. The basic research reveals that a wide variety of intracellular/cell surface molecules, cytokines, chemokines, and micro RNAs are involved in lymphomagenesis, and some of them are related to EBV. Understanding lymphoma behavior introduces new therapeutic strategies, such as the usage of immune checkpoint inhibitors, peptide vaccines, and molecular targeting therapy. This review addresses recent advances in basic and clinical aspects of ENKTL-NT, especially its relation to EBV features.
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36
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Jung JM, Yang HJ, Won CH, Chang SE, Lee MW, Lee WJ. Clinicopathological and prognostic study of primary cutaneous extranodal natural killer/T-cell lymphoma, nasal type: A systematic review. J Dermatol 2021; 48:1499-1510. [PMID: 34060130 DOI: 10.1111/1346-8138.15972] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/02/2021] [Accepted: 05/03/2021] [Indexed: 12/29/2022]
Abstract
Comprehensive studies of primary cutaneous extranodal natural killer/T-cell lymphoma (PCENKTL) are scarce. The objectives of this study are to describe PCENKTL in terms of its clinical features, histopathology, immunophenotypes, and prognosis, and to analyze factors affecting patient survival outcomes. We searched four databases and include studies with extractable data. We also searched the Asan Medical Center database for cases of PCENKTL. We include a total of 289 patients. The mean age at diagnosis was 52.8 years and the female to male ratio was 1:1.2. The most common clinical morphology was a subcutaneous nodule, followed by ulceration. About half of the patients presented with disseminated skin lesions. The median overall survival was 12.0 months and the 5-year survival rate was 22.0%. There was no correlation between the clinical morphology or the histopathological features of the skin lesions with the patient outcomes. Advanced TNM stage, a disseminated skin lesion, tumor location on the leg or trunk, the presence of B symptoms, and a high International Prognostic Index score were associated with a worse prognosis, and chemoradiotherapy was associated with a better survival outcome as compared with chemotherapy alone in univariable analyses. In multivariable analyses, only advanced TNM stage and tumor location on the leg were associated with a worse prognosis. In conclusion, PCENKTL is an aggressive cutaneous lymphoma and its prognosis is associated with TNM stage and tumor location.
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Affiliation(s)
- Joon Min Jung
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hee Joo Yang
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chong Hyun Won
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Eun Chang
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Mi Woo Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woo Jin Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Song MK, Chung JS, Oh SY, Lim SN, Lee WS, Lee SM, Kim DY. Clinical impact of lymphatic spread in patients with limited-stage upper aerodigestive tract NK/T cell lymphoma. Blood Res 2021; 56:72-78. [PMID: 34031274 PMCID: PMC8246034 DOI: 10.5045/br.2021.2020328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 03/01/2021] [Accepted: 03/19/2021] [Indexed: 11/17/2022] Open
Abstract
Background We investigated whether distancemax, that is, the degree of distance between the upper aerodigestive tract (UAT) mass and the farthest pathologic lymph node, was significantly associated with survival in patients with limited-stage UAT natural killer/T cell lymphoma (NKTCL). Methods A total of 157 patients who received chemotherapy (CTx) with/without radiotherapy (RTx) were enrolled. Results In the survival analysis, an elevated lactate dehydrogenase level [progression-free survival (PFS) hazard ratio (HR), 2.948; 95% confidence interval (CI), 1.606‒5.404; P<0.001; overall survival (OS) HR, 2.619; 95% CI, 1.594‒4.822; P=0.003], short distancemax (PFS HR, 0.170; 95% CI, 0.071‒0.410; P<0.001; OS HR, 0.142; 95% CI, 0.050‒0.402; P< 0.001), and CTx combined with RTx (HR, 0.168; 95%CI, 0.079‒0.380; P<0.001; OS HR, 0.193; 95% CI, 0.087‒0.429; P<0.001) had an independent predictive value for PFS and OS. Conclusion The evaluation of the degree of lymphatic spread and local control by CTx combined with RTx is essential in patients with limited-stage UAT NKTCL.
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Affiliation(s)
- Moo-Kon Song
- Department of Hematology, Hanyang University Hanmaeum Changwon Hospital, Changwon, Korea
| | - Joo-Seop Chung
- Department of Hematology-Oncology, Pusan National University Hospital Medical Research Institute, Busan, Korea
| | - Sung-Yong Oh
- Department of Oncology, Dong-A University Hospital, Busan, Korea
| | - Sung-Nam Lim
- Department of Hematology, Busan Haeundae Paik Hospital, Busan, Korea
| | - Won-Sik Lee
- Department of Hematology, Busan Paik Hospital, Busan, Korea
| | - Sang-Min Lee
- Department of Hematology, Busan Paik Hospital, Busan, Korea
| | - Do-Young Kim
- Department of Hematology-Oncology, Pusan National University Hospital Medical Research Institute, Busan, Korea
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Lee JY, Kim JH, Bang H, Cho J, Ko YH, Kim SJ, Kim WS. EGR1 as a potential marker of prognosis in extranodal NK/T-cell lymphoma. Sci Rep 2021; 11:10342. [PMID: 33990633 PMCID: PMC8121831 DOI: 10.1038/s41598-021-89754-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 04/19/2021] [Indexed: 12/11/2022] Open
Abstract
Extranodal natural killer T-cell lymphoma (ENKTL) is an aggressive malignancy with a dismal prognosis. In the present study, gene expression profiling was performed to provide more information on ENKTL molecular signature and offer a rationale for further investigation of prognostic markers in ENKTL. NanoString nCounter Analysis encompassing 133 target genes was used to compare gene expression levels of 43 ENKTL tumor samples. The majority of the patients were under 60 years of age (79.1%); 32 (74.4%) patients had nasal type ENKTL and 23 patients (53.5%) had intermediate/high risk ENKTL based on the prognostic index for natural killer cell lymphoma (PINK). The median follow-up was 15.9 months and the median overall survival (OS) was 16.1 months (95% CI 13.0-69.8). EGR1 upregulation was consistently identified in the localized stage with a low risk of prognostic index based on the PINK. Among the six significantly relevant genes for EGR1 expression, high expression levels of genes, including CD59, GAS1, CXCR7, and RAMP3, were associated with a good survival prognosis. The in vitro test showed EGR1 modulated the transcriptional activity of the target genes including CD59, GAS1, CXCR7, and RAMP3. Downregulation of EGR1 and its target genes significantly inhibited apoptosis and decreased chemosensitivity and attenuated radiation-induced apoptosis. The findings showed EGR1 may be a candidate for prognostic markers in ENKTL. Considerable additional characterization may be necessary to fully understand EGR1.
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Affiliation(s)
- Ji Yun Lee
- Division of Hematology-Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Joo Hyun Kim
- Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Heejin Bang
- Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Junhun Cho
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Hyeh Ko
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seok Jin Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Won Seog Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
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Zhang Y, Liu W, Zhang X, Wu B. Case Report: Primary NK/T Cell Lymphoma Nasal Type of the Colon With Multiple Intestinal Perforations. Front Oncol 2021; 11:577939. [PMID: 33816224 PMCID: PMC8010170 DOI: 10.3389/fonc.2021.577939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 02/22/2021] [Indexed: 02/05/2023] Open
Abstract
Background: Extranodal NK/T cell lymphoma is a rare non-Hodgkin lymphoma mainly involving the upper aerodigestive tract, even rarer is primary extranasal disease involving the intestine. We present a case of primary intestinal NK/T cell lymphoma with diagnostic challenge, which eventually developed into multiple intestinal perforations. Case Presentation: A 35-year-old man presented with diarrhea and recurrent fever. Abdominal CT revealed multi-segmental intestinal wall thickening. Colonoscopy showed multiple irregular ulcers in colon. During the hospitalization, the patient developed intestinal perforation and an emergency surgery was performed. The resected specimen showed multiple perforations of the colon. The surgical samples underwent pathological analysis, and a diagnosis of extranodal NK/T cell lymphoma nasal type was confirmed. After recovering from surgery, the patient started receiving chemotherapy and PD-1 monoclonal antibody. Fortunately, he was discharged after significant improvement in his general condition. Eleven months follow-up was uneventful. Conclusion: Early diagnosis of primary intestinal NK/T cell lymphoma is frequently difficult. Most patients were definitely diagnosed only after surgical resection following complications, resulting in a poor prognosis. Therefore, doctors should maintain high suspicion of this malignancy for early diagnosis at an early stage clinically.
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Affiliation(s)
- Yan Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Weiping Liu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Xinyue Zhang
- Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Bing Wu
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
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A composite single-nucleotide polymorphism prediction signature for extranodal natural killer/T-cell lymphoma. Blood 2021; 138:452-463. [PMID: 33728448 DOI: 10.1182/blood.2020010637] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 03/04/2021] [Indexed: 02/06/2023] Open
Abstract
Current prognostic scoring systems based on clinicopathologic variables are inadequate in predicting the survival and treatment response of extranodal natural killer/T-cell lymphoma (ENKTL) patients undergoing non-anthracyline-based treatment. We aimed to construct a classifier based on single-nucleotide polymorphisms (SNPs) for improving predictive accuracy and guiding clinical decision-making. The data of 722 patients with ENKTL from international multicenters were analyzed. A 7-SNP-based classifier was constructed using LASSO Cox regression in the training cohort (n=336) and further validated in the internal testing (n=144) and two external validation cohorts (n=142; n=100). The 7-SNP-based classifier showed good prognostic predictive efficacy in the training cohort and the three validation cohorts. Patients with high and low risk scores calculated by the classifier exhibited significantly different progression-free survival (PFS) and overall survival (OS) (all p<0.001). The 7-SNP-based classifier was further proved to be an independent prognostic factor by multivariate analysis, and its predictive accuracy was significantly better than clinicopathological risk variables. The application of the 7-SNP-based classifier was not affected by sample types. Notably, chemotherapy combined with radiotherapy significnalty improved PFS and OS versus radiotherapy alone in high risk Ann Anbor stage I patients, while there was no statistical difference between the two therapeutic modalities among low risk patients. A nomogram was constructed comprised of the classifier and clinicopathological variables, and showed remarkably better predictive accuracy than that of each variable alone. The 7-SNP-based classifier is a complement to existing risk stratification systems in ENKTL, which could have significant implications for clinical decision-making for ENKTL patients.
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Li J, Li J, Zhong M, Zhou H, Yu B. The Clinical Features and Survival Outcome of 107 Newly Diagnosed Advanced Stage Extranodal NK/T-Cell Lymphoma Cases: A Triple-Center Study. Cancer Manag Res 2021; 13:1541-1549. [PMID: 33623433 PMCID: PMC7896804 DOI: 10.2147/cmar.s292293] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 01/13/2021] [Indexed: 11/23/2022] Open
Abstract
Objective Advanced stage extranodal natural killer/T-cell lymphoma (ENKTL) is a distinct type of non-Hodgkin lymphoma and the prognosis of ENKTL is poor with current treatment. This study aimed to investigate the clinical features, treatment strategy and survival outcome in patients with advanced stage ENKTL. Patients and Methods A total of 107 patients with newly diagnosed advanced stage ENKTL between January 2010 and December 2014 were reviewed from three cancer centers. Survival probability was calculated using Kaplan-Meier and the survival curves were compared by Log rank test. Cox regression analyses was performed to investigate the prognostic factors in ENKTL. Results The median patient age in our cohort was 42.0 years, with a male to female ratio of around 2.3:1. Over half of the patients had B symptoms (n = 61), high IPI scores (≥ 2, n = 60) and high Prognostic Index of Natural Killer Lymphoma (PINK) scores (≥ 3, n = 69). Elevated LDH level was present in around half of the patients (44/91). Most patients (n = 88) in our cohort originated in upper aerodigestive tract and the remaining 19 cases presented with non-upper aerodigestive tract involvement at first diagnosis. Chemotherapy regimens used in our study mainly include CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (n = 26), L-asparaginase (L-asp) containing chemotherapy (GELOXD (gemcitabine, l-asparaginase, oxaliplatin and dexamethasone) and SMILE (L-asparaginase, methotrexate, ifosfamide, etoposide, and dexamethasone)) (n = 66). No significant difference between the baseline clinical characteristics was found between the L-asp and CHOP group. The CR rate after treatment was 39.3% (42/107) for the whole cohort. The 3-year progression-free survival (PFS) and 3-year overall survival (OS) rate was 41.0% and 41.5%, respectively. The 3-year PFS (49.2% vs 26.5%, P = 0.048) and 3-year OS (49.4% vs 26.0%, P = 0.030) was significantly higher in the L-asp group than the CHOP group. Patient CR status and PINK score were proved to be significant independent factors affecting OS and PFS by multivariate analysis. The grade 3/4 hematologic toxicity (P = 0.0003) and non-hematologic toxicity (P = 0.0002) occurred more frequently in the SMILE group than the GELOXD group. Conclusion Our results demonstrated that L-asp containing chemotherapy could provide favorable survival outcomes in patients with advanced stage ENKTL.
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Affiliation(s)
- Jiwei Li
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.,Institute of Pathology, Fudan University, Shanghai, 200032, People's Republic of China
| | - Jin Li
- Department of Lymphoma and Hematology, Hunan Cancer Hospital, Changsha, People's Republic of China.,Department of Lymphoma and Hematology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
| | - Meizuo Zhong
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Hui Zhou
- Department of Lymphoma and Hematology, Hunan Cancer Hospital, Changsha, People's Republic of China.,Department of Lymphoma and Hematology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
| | - Baohua Yu
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.,Institute of Pathology, Fudan University, Shanghai, 200032, People's Republic of China
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Peng YY, Xiong YY, Zhang LX, Wang J, Zhang HB, Xiao Q, Guo SL. Allogeneic Hematopoietic Stem Cell Transplantation in Extranodal Natural Killer/T-cell Lymphoma. Turk J Haematol 2021; 38:126-137. [PMID: 33535731 PMCID: PMC8171200 DOI: 10.4274/tjh.galenos.2021.2020.0438] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Objective Extranodal NK/T-cell lymphoma (ENKL) is aggressive and resistant to chemotherapy and radiotherapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for high-risk lymphomas owing to its associated graft-versus-lymphoma (GVL) effect. However, its application to ENKL is limited. We aim to summarize the characteristics of allo-HSCT for ENKL and, more importantly, evaluate whether allo-HSCT could offer any benefits for ENKL. Materials and Methods A systematic review and data analysis were performed to evaluate the performance of allo-HSCT in the treatment of ENKL using studies obtained from PubMed, Medline, and Embase from January 2000 to December 2019 in the English language. Results A total of 136 cases from 17 eligible publications were included in this study. It was found that after allo-HSCT, with an average follow-up time of 34 months (range: 1-121 months), 37.5% (52) of 136 patients had acute graft-versus-host disease (GVHD) and 31.6% (43) had chronic GVHD. Furthermore, 35.3% (48) of the patients were reported to have relapsed, but 2 of those relapsed only locally and achieved complete remission (CR) again with additional irradiation, chemotherapy, and donor lymphocyte infusions for one and rapid tapering and discontinuation of cyclosporine for the other, earning more than one year of extra survival. Finally, of the 136 patients, 51.5% (70) died because of primary disease progression (42.9%), infection (20.0%), GVHD (11.4%), organ failure (7.1%), hemorrhage (4.3%), and other causes (not specified/unknown) (14.3%). Conclusion Allo-HSCT may be a treatment option for advanced or relapsed/refractory ENKL, but its role still requires more rigorous future studies.
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Affiliation(s)
- Yin-yin Peng
- First Affiliated Hospital of Chongqing Medical University, Department of Hematology, Chongqing, China
| | - Yi-ying Xiong
- First Affiliated Hospital of Chongqing Medical University, Department of Hematology, Chongqing, China
| | - Li-xia Zhang
- First Affiliated Hospital of Chongqing Medical University, Department of Hematology, Chongqing, China
| | - Jing Wang
- First Affiliated Hospital of Chongqing Medical University, Department of Hematology, Chongqing, China
| | - Hong-bin Zhang
- First Affiliated Hospital of Chongqing Medical University, Department of Hematology, Chongqing, China
| | - Qing Xiao
- First Affiliated Hospital of Chongqing Medical University, Department of Hematology, Chongqing, China
| | - Shu-liang Guo
- First Affiliated Hospital of Chongqing Medical University, Department of Respiratory Medicine, Chongqing, China
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Li H, Shao G, Zhang Y, Chen X, Du C, Wang K, Gao Z. Nomograms based on SUVmax of 18F-FDG PET/CT and clinical parameters for predicting progression-free and overall survival in patients with newly diagnosed extranodal natural killer/T-cell lymphoma. Cancer Imaging 2021; 21:9. [PMID: 33419476 PMCID: PMC7796613 DOI: 10.1186/s40644-020-00379-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 12/29/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The prognostic value of 18F-FDG PET/CT in extranodal natural killer/T-cell lymphoma (ENKTL) is not well established. We aimed to develop nomograms for individualized estimates of progression-free survival (PFS) and overall survival (OS) in patients with ENKTL using 18F-FDG PET/CT parameters and clinical parameters. METHODS A total of 171 patients with newly diagnosed ENKTL undergoing 18F-FDG PET/CT scanning were retrospectively analyzed. Nomograms were constructed according to multivariate Cox proportional hazards regression. The predictive and discriminatory capacities of the nomograms were then measured using the concordance index (C-index), calibration plots, and Kaplan-Meier curves. The C-index, the area under receiver operating characteristic (ROC) curve (AUC), and decision curve analysis (DCA) were used to contrast the predictive and discriminatory capacities of the nomograms against with the International Prognostic Index (IPI) and Korean Prognostic Index (KPI). RESULTS Multivariate analysis demonstrated that pretreatment SUVmax≥9.5, disease stage II and III-IV, elevated lactate dehydrogenase (LDH), and elevated β2-microglobulin (β2-MG) had the strongest association with unfavorable PFS and OS. In addition, hemoglobin (Hb) < 120 g/L had a tendency to be associated with PFS. Both nomogram models incorporated SUVmax, Ann Arbor stage, LDH, and β2-MG. The PFS nomogram also included Hb. The nomograms showed good prediction accuracies, with the C-indexes for PFS and OS were 0.729 and 0.736, respectively. The calibration plots for 3-year and 5-year PFS/OS reported good consistency between predicted and observed probabilities for survival time. The PFS and OS were significantly different according to tertiles of nomogram scores (p < 0.001). The C-index and AUCs of the nomograms were higher than that of IPI and KPI. Moreover, DCA showed that the predictive accuracy of the nomograms for PFS and OS were both higher than that of IPI and KPI. CONCLUSIONS This study established nomograms that incorporate pretreatment SUVmax and clinical parameters, which could be effective tools for individualized prognostication of both PFS and OS in patients with newly diagnosed ENKTL.
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Affiliation(s)
- Hongyan Li
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Guozhu Shao
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022 China
| | - Yajing Zhang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Xiaomin Chen
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Chengcheng Du
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Kun Wang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Zairong Gao
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
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Yan Z, Yao S, Liu Y, Zhang J, Li P, Wang H, Chu J, Zhao S, Yao Z. Durable Response to Sintilimab and Chidamide in a Patient With Pegaspargase- and Immunotherapy-Resistant NK/T-Cell Lymphoma: Case Report and Literature Review. Front Oncol 2020; 10:608304. [PMID: 33363038 PMCID: PMC7759664 DOI: 10.3389/fonc.2020.608304] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 11/09/2020] [Indexed: 12/17/2022] Open
Abstract
The prognosis of patients with relapsed/refractory NK/T-cell lymphoma (NKTCL) is dismal. Immunotherapy has showed encouraging anti-tumor activity in patients with asparaginase-resistant NKTCL; however, only a portion of patients benefit and the median response duration is rather short. Treatment strategies have not been identified for immunotherapy-resistant NKTCL. We describe a patient with primary cutaneous NKTCL experienced disease progression after pegaspargase-based chemotherapy and PD-1 inhibitor (sintilimab)-based immunotherapy. Following a combined treatment of sintilimab and the HDAC inhibitor chidamide, the patient achieved a durable complete molecular response with mild toxicity. This case indicates that the combination of PD-1 inhibitor and HDAC inhibitor might be a treatment choice for immunotherapy-resistant NKTCL.
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Affiliation(s)
- Zheng Yan
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Shuna Yao
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Yanyan Liu
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Jianbo Zhang
- Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Peng Li
- The PET-CT Center of Henan Province, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Haiying Wang
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Junfeng Chu
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Shuang Zhao
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Zhihua Yao
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
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Lungu M, Telehuz A, Voinescu DC, Sapira V, Trifan A, Elkan EM, Fătu A, Creangă VZ, Polinschi M, Stoleriu G, Niculet E. NK/T-cell non-Hodgkin lymphoma: Case report and review of the literature. Exp Ther Med 2020; 21:91. [PMID: 33363602 PMCID: PMC7725024 DOI: 10.3892/etm.2020.9523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 10/26/2020] [Indexed: 11/25/2022] Open
Abstract
Natural killer (NK)/T-cell lymphomas represent a rare type of lymphoid malignancy with mostly extranodal involvement, having NK cell or (rare) T cell lineage, classified by the World Health Organization into several subtypes which can involve the head and neck region, with the most frequent one being the nasal type. This article presents the case of a 31-year-old patient who presented at the Emergency Unit of Saint Andrew Emergency Clinical Hospital of Galati suffering from mycosis fungoides-like cutaneous lesions, associated with partial left eyelid ptosis of unknown etiology, as well as a poor health status with fever and respiratory failure. The final diagnosis was NK/T-cell non-Hodgkin lymphoma, possibly nasal type with medium sized T cells. The complexity of the rare diagnosis, associated with the unusual rapid patient evolution towards exitus 3 months after diagnosis, the intra-orbital metastatic involvement and the absence of a standardized treatment are case peculiarities, some of which are consistent with current literature data.
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Affiliation(s)
- Mihaiela Lungu
- Clinical Department, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Anca Telehuz
- Research Center of Medical and Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Doina Carina Voinescu
- Clinical Department, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Violeta Sapira
- Clinical Department, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Angel Trifan
- Research Center of Medical and Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Eva Maria Elkan
- Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Ana Fătu
- Research Center of Medical and Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Valerica Zărnescu Creangă
- Research Center of Medical and Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Mihai Polinschi
- Research Center of Medical and Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Gabriela Stoleriu
- Clinical Department, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Elena Niculet
- Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
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Chen Z, Fang X, Huang H, Wang Z, Hong H, Chen M, Ren Q, Yao Y, Zhang L, Tian Y, Lin S, Lin T. A proposal for a prognostic index for non-nasal type natural killer/T cell lymphoma after asparaginase-based treatment. Ann Hematol 2020; 99:2811-2819. [PMID: 32975588 DOI: 10.1007/s00277-020-04278-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 09/17/2020] [Indexed: 11/27/2022]
Abstract
In the era of asparaginase-based therapy for extranodal natural killer/T cell lymphoma (ENKTL), the clinical outcomes of ENKTL have notably improved. However, as a rare subtype of ENKTL, the therapeutic effect and prognostic factors of non-nasal type ENKTL remain unclear. Thus, we performed this study to analyze the clinical characteristics and to establish a prognostic model specifically for the non-nasal disease. We performed a retrospective study of consecutive patients newly diagnosed with non-nasal type ENKTL and mainly received asparaginase-based therapy at Sun Yat-sen University Cancer Center (SYSUCC) between January 2011 and December 2019, to analyze the prognostic factors and to propose a prognostic model. We validated the prognostic model in an independent cohort. In total, 98 non-nasal type ENKTL patients were included in the training cohort. Multivariate analyses showed that prognostic factors for OS were elevated LDH levels, involvement of bone marrow and serum total protein (TP) < 60 g/L. We developed a new prognostic model named the non-nasal type ENKTL prognostic index (NPI) by grouping the prognostic factors: group 1, no risk factors; group 2, one risk factor; and group 3, two or three risk factors, which were associated with 3-year OS rates of 84.1% (95% CI, 70.9-97.2), 46.8% (27.7-65.8), and 14.9% (0-32.9), respectively (P < 0.001). These results were validated and confirmed in an independent cohort. The new model is efficient in distinguishing non-nasal-type ENKTL patients with various outcomes in the contemporary era of asparaginase-based therapy.
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Affiliation(s)
- Zegeng Chen
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Xiaojie Fang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - He Huang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Zhao Wang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Huangming Hong
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Meiting Chen
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Quanguang Ren
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Yuyi Yao
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Limei Zhang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Ying Tian
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Suxia Lin
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Tongyu Lin
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. .,Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, China.
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Allogeneic stem cell transplantation for patients with aggressive NK-cell leukemia. Bone Marrow Transplant 2020; 56:347-356. [PMID: 32778688 DOI: 10.1038/s41409-020-01009-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 06/18/2020] [Accepted: 07/21/2020] [Indexed: 11/08/2022]
Abstract
Aggressive NK-cell leukemia (ANKL) has a fulminant clinical course with a poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment. Using the Japanese transplant registry data, the outcomes of 59 ANKL patients who underwent first allo-HSCT were analyzed. Twenty-nine patients received stem cells from cord blood (CB), 18 from peripheral blood, and 12 from bone marrow. At the time of transplant 21 patients had complete response (CR), and 7 partial response (PR), but 31 without response. The 1-year and 5-year overall survival (OS) were 33.9% and 27.3%, respectively. The 1-year cumulative incidences of relapse or progression was 55.5%, and that of non-relapse mortality was 12.1%. The OS was significantly better for patients with CR or PR at the time of allo-HSCT (P = 0.046), which was equivalent to that for patients who experienced primary induction failure at the time of allo-HSCT but achieved CR afterwards (40.6% versus 32.0% at 5 years; P = 0.95). Patients receiving CB had a significantly better OS than those receiving stem cells from others (37.3% versus 16.2% at 5 years; P = 0.04). Patients achieving event-free survival at 12 months after allo-HSCT had good outcomes with 5-year OS of 85.2%.
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Hong H, Li Y, Lim ST, Liang C, Huang H, Yi P, Wu T, Du X, Zhang M, Wang J, Zhu J, Liu T, Meng F, Wu G, Guo Y, Zhu Y, Zhao W, Jin J, Li J, Deng Y, Gu K, Wu X, Ke X, Xie D, Lin D, Peng Z, Wu J, Liu Q, Kim WS, Lin T. A proposal for a new staging system for extranodal natural killer T-cell lymphoma: a multicenter study from China and Asia Lymphoma Study Group. Leukemia 2020; 34:2243-2248. [PMID: 32066865 PMCID: PMC7387308 DOI: 10.1038/s41375-020-0740-1] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 01/16/2020] [Accepted: 02/03/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Huangming Hong
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
- Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yexiong Li
- Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Soon Thye Lim
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Chaoyong Liang
- Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - He Huang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Pingyong Yi
- Department of Medical Oncology, Hunan Cancer Hospital, Changsha, China
| | - Tao Wu
- Department of Lymphoma-Oncology, Guizhou Cancer Hospital, Guiyang, Guizhou, China
| | - Xin Du
- Department of Hematology, Guangdong General Hospital, Guangzhou, China
| | - Mingzhi Zhang
- Department of Medical Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jinghua Wang
- Department of Medical Oncology, Nanjing General Hospital of Nanjing Military Command, Nanjing, China
| | - Jun Zhu
- Department of Lymphoma-Oncology, Peking University Cancer Hospital, Beijing, China
| | - Ting Liu
- Department of Hematology, West China Hospital of Sichuan University, Chengdu, China
| | - Fanyi Meng
- Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, China
| | - Gang Wu
- Department of Radiation Oncology, Wuhan Union Hospital, Wuhan, China
| | - Ye Guo
- Department of Medical Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yuan Zhu
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Weili Zhao
- Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Jin
- Department of Hematology, the First Affiliated Hospital Zhejiang University, Hangzhou, China
| | - Juan Li
- Department of Hematology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yanming Deng
- Department of Medical Oncology, the First People's Hospital of Foshan, Foshan, China
| | - Kangsheng Gu
- Department of Medical Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xiangyuan Wu
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaoyan Ke
- Department of Hematology, Peking University Third Hospital, Beijing, China
| | - Derong Xie
- Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Daren Lin
- Department of Medical Oncology, Jiangmen Central Hospital, Jiangmen, China
| | - Zhigang Peng
- Department of Medical Oncology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Junxin Wu
- Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, China
| | - Qing Liu
- Department of Epidemiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Won Seog Kim
- Division of Hematology Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tongyu Lin
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
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Yao N, Hou Q, Zhang S, Xiao H, Liang Y, Xu X, Guo R, Li H, Lan S, Si H, Cao J. Prognostic Nutritional Index, Another Prognostic Factor for Extranodal Natural Killer/T Cell Lymphoma, Nasal Type. Front Oncol 2020; 10:877. [PMID: 32637354 PMCID: PMC7317673 DOI: 10.3389/fonc.2020.00877] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 05/04/2020] [Indexed: 01/11/2023] Open
Abstract
Objective: The prognostic nutritional index (PNI) is a significant prognostic factor in diffuse large B cell lymphoma, follicular lymphoma, and other malignancies. The current study aimed to explore its prognostic role in extranodal natural killer/T cell lymphoma (ENKTL). Methods: Patients diagnosed with ENKTL and treated during 2002 and 2018 (n = 184) were retrospectively recruited. PNI was calculated from albumin concentration (g/L) and total lymphocyte count (*109/L). The association of PNI and overall survival (OS) or progression-free survival (PFS) was assessed in univariate analysis and multivariate Cox regression validated by the 10-fold cross-validation method. Results: Survival analyses showed that both OS and PFS differed significantly between PNI groups stratified by a cutoff value of 49.0. The 3- and 5-year OS were 42.5 and 36.3% in the low-PNI (PNI < 49) subgroup and 70.6% and 63.9% (P < 0.001) in the high-PNI (PNI ≥ 49) subgroup, respectively. The corresponding PFS showed a similar pattern (38.4, 32.4 vs. 64.8, 54.0%, P < 0.001). Multivariate analysis indicated that PNI was significantly independent for both OS (HR = 0.517, 95% CI = 0.322–0.831, P = 0.006) and PFS (HR = 0.579, 95% CI = 0.373–0.899, P = 0.015). Furthermore, integrating PNI into the models of IPI (International Prognostic Index), KPI (Korean Prognostic Index), and PINK (prognostic index of natural killer lymphoma) could improve the area under the curve (AUC) and reduce the integrated Brier score (IBS) and Akaike Information Criterion (AIC) value of each model. Conclusion: PNI was a significant prognostic indicator for ENKTL.
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Affiliation(s)
- Ningning Yao
- Department of Radiobiology, Shanxi Provincial Cancer Hospital, Taiyuan, China
| | - Qing Hou
- Department of Radiobiology, Shanxi Provincial Cancer Hospital, Taiyuan, China
| | - Shuangping Zhang
- Department of Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, China
| | - Huan Xiao
- Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yu Liang
- Department of Radiotherapy, Shanxi Provincial Cancer Hospital, Taiyuan, China
| | - Xiaokai Xu
- Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Ruyuan Guo
- Department of Radiotherapy, Shanxi Provincial Cancer Hospital, Taiyuan, China
| | - Hongwei Li
- Department of Radiotherapy, Shanxi Provincial Cancer Hospital, Taiyuan, China
| | - Shengmin Lan
- Department of Radiotherapy, Shanxi Provincial Cancer Hospital, Taiyuan, China
| | - Hongwei Si
- Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jianzhong Cao
- Department of Radiobiology, Shanxi Provincial Cancer Hospital, Taiyuan, China.,Department of Radiotherapy, Shanxi Provincial Cancer Hospital, Taiyuan, China
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Wei C, Cao X, Zhang W, Zhang Y, Wang W, Zhang L, Yang C, Feng J, Cai H, Chen M, Mao Y, Zhou D. Combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase (GDP-ML) for patients with newly diagnosed extranodal natural killer/T cell lymphoma, nasal type: a single arm, single center, prospective phase 2 study. Ann Hematol 2020; 99:2801-2809. [PMID: 32399707 DOI: 10.1007/s00277-020-04036-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 04/10/2020] [Indexed: 12/28/2022]
Abstract
Extranodal natural killer/T cell lymphoma, nasal type (ENKL) is a highly aggressive tumor with relatively poor prognosis. In this prospective study, we investigated the efficacy and toxicity of a novel GDP-ML regimen (combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase) as front-line treatment in newly diagnosed ENKL. Eligible newly diagnosed stage I/II ENKL patients received sandwich chemoradiation therapy. Patients with stage III/IV disease received an initial 4 cycles of GDP-ML regimen. After 4 cycles, responding patients continued to receive either autologous transplantation or additional two courses of GDP-ML. A total of 44 patients were enrolled with a median follow-up of 26 months. The overall response rate (ORR) were 78.6% for the whole cohort, 84.6% for stage I/II, and 66.7% for stage III/IV, and corresponding complete remission (CR) rates were 61.9%, 76.9%, and 33.3%. The 1- year and 2- year progression-free survival (PFS) rates were 69.3% and 62.9%, and 1- year and 2-year overall survival (OS) rates were 76.5% and 67.4%, respectively. Patients with stage I/II disease showed better 2-year OS rate compared with stage III/IV patients (88.1% vs. 33.2%, p < 0.001). Patients who achieved CR had significantly better 2-year OS rate compared with non-CR patients (90.8% vs. 24.5%, p < 0.001). The main adverse event was hematologic toxicity. Grade 3/4 neutropenia occurred in 59.1% of patients. These results indicate that GDP-ML is an effective and well-tolerated induction regimen with newly diagnosed ENKL patients. This clinical trial was registered on www.chictr.org.cn (ChiCTR-ONC-12002055).
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Affiliation(s)
- Chong Wei
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Xinxin Cao
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Wei Zhang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Yan Zhang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Wei Wang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Lu Zhang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Chen Yang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Jun Feng
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Huacong Cai
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Miao Chen
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Yueying Mao
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Daobin Zhou
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
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