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S H, Sudarsan SS, Anbarasan S, Sankar S. Unusual Presentation of Non-Hodgkin Lymphoma of Two Cases: Case Report. Indian J Otolaryngol Head Neck Surg 2024; 76:3717-3721. [PMID: 39130249 PMCID: PMC11306709 DOI: 10.1007/s12070-024-04719-3] [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: 03/29/2024] [Accepted: 04/18/2024] [Indexed: 08/13/2024] Open
Abstract
Lymphomas are a diverse group of neoplastic disorders arising primarily in lymph nodes. They have been majorly classified into Hodgkin and Non-Hodgkin lymphomas(NHL). NHL can be of B, T and Null cell categories having further subtypes based on their histological characteristics. Lymphomas can be nodal and extra nodal. The head and neck area are the second most common site of extra nodal lymphoma, with tonsils being the most common site of involvement; other sites include the nasopharynx and tongue base. B- Cell type being the most common type. Predominantly occurs in elderly. Presentations depends on the site involved. Various modalities like surgical treatment, chemotherapy (or) radiotherapy is available. Each stage has varied survival rates and prognosis and responses to the treat depending on the patient factors. In this paper, we report two cases of patients with non-Hodgkin lymphoma of tonsil, where the preoperative clinical diagnosis and radiological diagnosis was inconclusive and final diagnosis was established based on histopathological examination.
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Affiliation(s)
- Haritha S
- Department of Otorhinolaryngology, Head and Neck Surgery, Saveetha Medical College and Hospital, SIMATS, Saveetha University, Saveetha Nagar, Thandalam, Chennai, 602105 Tamil Nadu India
| | - Shyam Sudhakar Sudarsan
- Department of Otorhinolaryngology, Head and Neck Surgery, Saveetha Medical College and Hospital, SIMATS, Saveetha University, Saveetha Nagar, Thandalam, Chennai, 602105 Tamil Nadu India
| | - Subagar Anbarasan
- Department of Otorhinolaryngology, Head and Neck Surgery, Saveetha Medical College and Hospital, SIMATS, Saveetha University, Saveetha Nagar, Thandalam, Chennai, 602105 Tamil Nadu India
| | - Sakthimurugan Sankar
- Department of Otorhinolaryngology, Head and Neck Surgery, Saveetha Medical College and Hospital, SIMATS, Saveetha University, Saveetha Nagar, Thandalam, Chennai, 602105 Tamil Nadu India
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Jing F, Liu Y, Zhao X, Wang N, Dai M, Chen X, Zhang Z, Zhang J, Wang J, Wang Y. Baseline 18F-FDG PET/CT radiomics for prognosis prediction in diffuse large B cell lymphoma. EJNMMI Res 2023; 13:92. [PMID: 37884763 PMCID: PMC10603012 DOI: 10.1186/s13550-023-01047-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 10/22/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. Standard treatment includes chemoimmunotherapy with R-CHOP or similar regimens. Despite treatment advancements, many patients with DLBCL experience refractory disease or relapse. While baseline 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) parameters have shown promise in predicting survival, they may not fully capture lesion heterogeneity. This study aimed to assess the prognostic value of baseline 18F-FDG PET radiomics features in comparison with clinical factors and metabolic parameters for assessing 2-year progression-free survival (PFS) and 5-year overall survival (OS) in patients with DLBCL. RESULTS A total of 201 patients with DLBCL were enrolled in this study, and 1328 radiomics features were extracted. The radiomics signatures, clinical factors, and metabolic parameters showed significant prognostic value for individualized prognosis prediction in patients with DLBCL. Radiomics signatures showed the lowest Akaike information criterion (AIC) value and highest Harrell's concordance index (C-index) value in comparison with clinical factors and metabolic parameters for both PFS (AIC: 571.688 vs. 596.040 vs. 576.481; C-index: 0.732 vs. 0.658 vs. 0.702, respectively) and OS (AIC: 339.843 vs. 363.671 vs. 358.412; C-index: 0.759 vs. 0.667 vs. 0.659, respectively). Statistically significant differences were observed in the area under the curve (AUC) values between the radiomics signatures and clinical factors for both PFS (AUC: 0.768 vs. 0.681, P = 0.017) and OS (AUC: 0.767 vs. 0.667, P = 0.023). For OS, the AUC of the radiomics signatures were significantly higher than those of metabolic parameters (AUC: 0.767 vs. 0.688, P = 0.007). However, for PFS, no significant difference was observed between the radiomics signatures and metabolic parameters (AUC: 0.768 vs. 0.756, P = 0.654). The combined model and the best-performing individual model (radiomics signatures) alone showed no significant difference for both PFS (AUC: 0.784 vs. 0.768, P = 0.163) or OS (AUC: 0.772 vs. 0.767, P = 0.403). CONCLUSIONS Radiomics signatures derived from PET images showed the high predictive power for progression in patients with DLBCL. The combination of radiomics signatures, clinical factors, and metabolic parameters may not significantly improve predictive value beyond that of radiomics signatures alone.
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Affiliation(s)
- Fenglian Jing
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
- Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, 050011, Hebei, China
| | - Yunuan Liu
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
- Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, 050011, Hebei, China
| | - Xinming Zhao
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China.
- Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, 050011, Hebei, China.
| | - Na Wang
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
- Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, 050011, Hebei, China
| | - Meng Dai
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
- Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, 050011, Hebei, China
| | - Xiaolin Chen
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
- Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, 050011, Hebei, China
| | - Zhaoqi Zhang
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
- Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, 050011, Hebei, China
| | - Jingmian Zhang
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
- Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, 050011, Hebei, China
| | - Jianfang Wang
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
- Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, 050011, Hebei, China
| | - Yingchen Wang
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
- Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, 050011, Hebei, China
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Xu PP, Shen R, Shi ZY, Cheng S, Wang L, Liu Y, Zhang L, Huang R, Ma X, Wu X, Yao H, Yu Y, Zhao WL. The Prognostic Significance of CD79B Mutation in Diffuse Large B-Cell Lymphoma: A Meta-analysis and Systematic Literature Review. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2022; 22:e1051-e1058.e1. [PMID: 36182550 DOI: 10.1016/j.clml.2022.08.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/29/2022] [Accepted: 08/16/2022] [Indexed: 01/26/2023]
Abstract
INTRODUCTION Previous studies have shown that diffuse large B-cell lymphoma (DLBCL) subtype with both B-cell antigen receptor complex-associated protein beta chain (CD79B) and myeloid differentiation primary response 88 mutations (MYD88) had inferior outcome under standard immunochemotherapy. However, the prognostic significance of CD79B alone in DLBCL has not been fully elucidated. We conducted a meta-analysis to investigate the role of CD79B mutation on overall survival (OS) in patients with DLBCL. METHODS We performed literature search in PubMed and Embase databases and followed PRISMA guidelines to select publications for analysis. The primary and secondary outcome was OS and progression-free survival (PFS) respectively. Hazard ratio (HR) for OS/PFS in CD79B mutant group with that in wild-type group in R-chemotherapy patients was either estimated using Cox proportional hazard model from the studies with individual participant level data or extracted from the original publication with aggregated results. RESULTS Nine eligible studies with survival information according to CD79B mutation status were included in this meta-analysis. The pooled hazard ratio for OS was 1.38 (95% CI, 1.13-1.70; p = 0.0021) for CD79B mutation, providing evidence that CD79B mutation was unfavorable prognostic factor for survival in DLBCL patients treated with immunochemotherapy. We identified the inferior prognostic impact of CD79B mutation was independent from well-established prognostic model in DLBCL, International Prognostic Index. The predictive power of CD79B mutation was stronger than that of MYD88 mutation. CONCLUSION This meta-analysis revealed that CD79B mutation could be a key biomarker for DLBCL disease progression and future mechanism-based target therapy in DLBCL needs to be studied.
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Affiliation(s)
- Peng-Peng Xu
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rong Shen
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zi-Yang Shi
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shu Cheng
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Wang
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai, China
| | - Yang Liu
- BeiGene (Shanghai) Co. Ltd., Shanghai, China
| | - Lu Zhang
- BeiGene (Shanghai) Co. Ltd., Shanghai, China
| | - Ruiqi Huang
- BeiGene (Shanghai) Co. Ltd., Shanghai, China
| | - Xiaopeng Ma
- BeiGene (Shanghai) Co. Ltd., Shanghai, China
| | - Xikun Wu
- BeiGene (Shanghai) Co. Ltd., Shanghai, China
| | - Hui Yao
- BeiGene (Shanghai) Co. Ltd., Shanghai, China
| | - Yiling Yu
- BeiGene (Shanghai) Co. Ltd., Shanghai, China
| | - Wei-Li Zhao
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai, China.
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Narayan Bendale Y, Kadam A, Patil A, Kantilal Birari‐Gawande P. Complete tumor regression with exclusive Ayurvedic rasayana regimen in high‐grade diffuse large B‐cell lymphoma: A case report. Clin Case Rep 2022; 10:e05696. [PMID: 35441028 PMCID: PMC9010597 DOI: 10.1002/ccr3.5696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 01/31/2022] [Accepted: 02/04/2022] [Indexed: 11/17/2022] Open
Abstract
We are presenting a case of 51‐year‐old female patient, diagnosed with high‐grade NHL‐DLBCL by PET‐CT scan. Immediately, she was started with Rasayana therapy, a specially designed anti‐cancer treatment regimen by our clinic. We observed significant clinical improvement and regression in tumor size in this patient after treatment.
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Jiang C, Li A, Teng Y, Huang X, Ding C, Chen J, Xu J, Zhou Z. Optimal PET-based radiomic signature construction based on the cross-combination method for predicting the survival of patients with diffuse large B-cell lymphoma. Eur J Nucl Med Mol Imaging 2022; 49:2902-2916. [PMID: 35146578 DOI: 10.1007/s00259-022-05717-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 02/01/2022] [Indexed: 12/12/2022]
Abstract
PURPOSE To develop and externally validate models incorporating a PET radiomics signature (R-signature) obtained by the cross-combination method for predicting the survival of patients with diffuse large B-cell lymphoma (DLBCL). METHODS A total of 383 patients with DLBCL from two medical centres between 2011 and 2019 were included. The cross-combination method was used on three types of PET radiomics features from the training cohort to generate 49 feature selection-classification candidates based on 7 different machine learning models. The R-signature was then built by selecting the optimal candidates based on their progression-free survival (PFS) and overall survival (OS). Cox regression analysis was used to develop the survival prediction models. The calibration, discrimination, and clinical utility of the models were assessed and externally validated. RESULTS The R-signatures determined by 12 and 31 radiomics features were significantly associated with PFS and OS, respectively (P<0.05). The combined models that incorporated R-signatures, metabolic metrics, and clinical risk factors exhibited significant prognostic superiority over the clinical models, PET-based models, and the National Comprehensive Cancer Network International Prognostic Index in terms of both PFS (C-index: 0.801 vs. 0.732 vs. 0.785 vs. 0.720, respectively) and OS (C-index: 0.807 vs. 0.740 vs. 0.773 vs. 0.726, respectively). For external validation, the C-indices were 0.758 vs. 0.621 vs. 0.732 vs. 0.673 and 0.794 vs. 0.696 vs. 0.781 vs. 0.708 in the PFS and OS analyses, respectively. The calibration curves showed good consistency, and the decision curve analysis supported the clinical utility of the combined model. CONCLUSION The R-signature could be used as a survival predictor for DLBCL, and its combination with clinical factors may allow for accurate risk stratification.
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Affiliation(s)
- Chong Jiang
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210000, China
| | - Ang Li
- The Key Laboratory of Broadband Wireless Communication and Sensor Network Technology (Ministry of Education), Nanjing University of Posts and Telecommunications, Nanjing, China
| | - Yue Teng
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210000, China
| | - Xiangjun Huang
- The Key Laboratory of Broadband Wireless Communication and Sensor Network Technology (Ministry of Education), Nanjing University of Posts and Telecommunications, Nanjing, China
| | - Chongyang Ding
- Department of Nuclear Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Jianxin Chen
- The Key Laboratory of Broadband Wireless Communication and Sensor Network Technology (Ministry of Education), Nanjing University of Posts and Telecommunications, Nanjing, China.
| | - Jingyan Xu
- Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210000, China.
| | - Zhengyang Zhou
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210000, China.
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RAJABATO W, CHANDIKA V, HARAHAP AS. Unilateral Tonsillar Swelling as a Manifestation of Diffuse Large B Cell Lymphoma (DLBCL): Case Report. MAEDICA 2021; 16:750-752. [PMID: 35261684 PMCID: PMC8897779 DOI: 10.26574/maedica.2020.16.4.750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Approximately 30-40% of all diffuse large B-cell lymphoma (DLBCL) cases, which have initially been present in extranodal sites with the most common involvement, were found at the level of the gastrointestinal tract (34%), head and neck (13.6%), and skin/soft tissue (10.6%). More than half of head and neck lymphomas occur in the Waldeyer ring, with 40% to 50% of these arising from the tonsil. The majority of tonsil lymphomas are B-cell origin, and DLBCL is the most common histological type. Here we presented a case of tonsillar DLBCL with long-term complete remission after R-CHOP treatment.
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Affiliation(s)
- Wulyo RAJABATO
- Division of Hematology-Medical Oncology, Department of Internal Medicine, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine Universitas Indonesia
| | - Vitya CHANDIKA
- Division of Hematology-Medical Oncology, Department of Internal Medicine, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine Universitas Indonesia
| | - Agnes Stephanie HARAHAP
- Department of Anatomical Pathology, Dr. Cipto Mangunkusumo General Hospital/ Faculty of Medicine Universitas Indonesia
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Lee CH, Jeon SY, Yhim HY, Kwak JY. Disseminated soft tissue diffuse large B-cell lymphoma involving multiple abdominal wall muscles: A case report. World J Clin Cases 2021; 9:8557-8562. [PMID: 34754868 PMCID: PMC8554429 DOI: 10.12998/wjcc.v9.i28.8557] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 06/23/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and patients with DLBCL typically present rapidly growing masses. Lymphoma involving muscle is rare and accounts for only 5%; furthermore, multiple muscles and soft tissue involvement of DLBCL is unusual. Due to unusual clinical manifestation, accurate diagnosis could be delayed.
CASE SUMMARY A 61-year-old man complained of swelling, pain and erythematous changes in the lower abdomen. Initially, soft tissue infection was suspected, however, skin lesion did not respond to antibiotics. 18Fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography-computed tomography demonstrated FDG uptake not only in the skin and subcutaneous tissue of the abdomen but also in the abdominal wall muscles, peritoneum, perineum, penis and testis. DLBCL was confirmed by biopsy of the abdominal wall muscle and subcutaneous tissue. After intensive treatment including chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone, central nervous system prophylaxis (intrathecal injection of methotrexate, cytarabine and hydrocortisone) and orchiectomy, he underwent peripheral blood stem cell mobilization for an autologous hematopoietic stem cell transplantation. Despite intensive treatment, the disease progressed rapidly and the patient showed poor outcome (overall survival, 9 mo; disease free survival, 3 mo).
CONCLUSION The first clinical manifestation of soft tissue DLBCL involving multiple muscles was similar to the infection of the soft tissue.
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Affiliation(s)
- Chang-Hoon Lee
- Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - So-Yeon Jeon
- Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - Ho-Young Yhim
- Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - Jae-Yong Kwak
- Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
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The Role of Physical Therapy Following CAR T-Cell Therapy. JOURNAL OF ACUTE CARE PHYSICAL THERAPY 2021. [DOI: 10.1097/jat.0000000000000183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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de Carvalho PS, Leal FE, Soares MA. Clinical and Molecular Properties of Human Immunodeficiency Virus-Related Diffuse Large B-Cell Lymphoma. Front Oncol 2021; 11:675353. [PMID: 33996608 PMCID: PMC8117347 DOI: 10.3389/fonc.2021.675353] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 04/14/2021] [Indexed: 12/15/2022] Open
Abstract
Non-Hodgkin lymphoma is the most common malignancy affecting people living with HIV (PLWH). Among its several subtypes, diffuse large B-cell lymphoma (DLBCL) is an important manifestation within the HIV-infected compartment of the population. Since HIV is able to modulate B cells and promote lymphomagenesis through direct and indirect mechanisms, HIV-related DLBCL has specific characteristics. In this review, we address the clinical and molecular properties of DLBCL disease in the context of HIV infection, as well as the mechanisms by which HIV is able to modulate B lymphocytes and induce their transformation into lymphoma.
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Affiliation(s)
- Pedro S de Carvalho
- Programa de Oncovirologia, Instituto Nacional do Câncer, Rio de Janeiro, Brazil
| | - Fabio E Leal
- Programa de Oncovirologia, Instituto Nacional do Câncer, Rio de Janeiro, Brazil
| | - Marcelo A Soares
- Programa de Oncovirologia, Instituto Nacional do Câncer, Rio de Janeiro, Brazil.,Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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First-Line Treatment for Primary Breast Diffuse Large B-Cell Lymphoma Using Immunochemotherapy and Central Nervous System Prophylaxis: A Multicenter Phase 2 Trial. Cancers (Basel) 2020; 12:cancers12082192. [PMID: 32781541 PMCID: PMC7463683 DOI: 10.3390/cancers12082192] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 07/31/2020] [Accepted: 08/03/2020] [Indexed: 11/17/2022] Open
Abstract
There are limited data from prospective controlled trials regarding optimal treatment strategies in patients with primary breast diffuse large B-cell lymphoma (DLBCL). In this phase 2 study (NCT01448096), we examined the efficacy and safety of standard immunochemotherapy and central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX). Thirty-three patients with newly diagnosed primary breast DLBCL received six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and four fixed doses of IT-MTX (12 mg). The median age was 50 years (range, 29-75), and all patients were females. According to the CNS-International Prognostic Index, most patients (n = 28) were categorized as the low-risk group. Among the 33 patients, 32 completed R-CHOP, and 31 completed IT-MTX as planned. With a median follow-up of 46.1 months (interquartile range (IQR), 31.1-66.8), the 2-year progression-free and overall survival rates were 81.3% and 93.5%, respectively. Six patients experienced treatment failures, which included the CNS in four patients (two parenchyma and two leptomeninges) and breast in two patients (one ipsilateral and one contralateral). The 2-year cumulative incidence of CNS relapse was 12.5%. Although standard R-CHOP and IT-MTX without routine radiotherapy show clinically meaningful survival outcomes, this strategy may not be optimal for reducing CNS relapse and warrants further investigation.
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Early risk stratification for diffuse large B-cell lymphoma integrating interim Deauville score and International Prognostic Index. Ann Hematol 2019; 98:2739-2748. [PMID: 31712879 DOI: 10.1007/s00277-019-03834-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 10/28/2019] [Indexed: 10/25/2022]
Abstract
The aim of this study was to evaluate the prognostic relevance of early risk stratification in diffuse large B-cell lymphoma (DLBCL) using interim Deauville score on positron emission tomography-computed tomography (PET-CT) scan and baseline International Prognostic Index (IPI). This retrospective study included 220 patients (median age, 64 years; men, 60%) diagnosed with DLBCL between 2007 and 2016 at our institution, treated with rituximab-based chemotherapy. Interim PET-CT was performed after three cycles of immuno-chemotherapy. Interim Deauville score was assessed as 4 or 5 in 49 patients (22.3%), and 94 patients (42.7%) had high-intermediate or high-risk IPI scores. In multivariate analysis, interim Deauville score (1-3 and 4-5) and baseline IPI (low/low-intermediate and high-intermediate/high) were independently associated with progression-free survival (for Deauville score, hazard ratio [HR], 1.00 vs. 2.96 [95% confidence interval (CI), 1.83-4.78], P < 0.001; for IPI, HR, 1.00 vs. 4.84 [95% CI, 2.84-8.24], P < 0.001). We stratified patients into three groups: low-risk (interim Deauville scores 1-3 and low/low-intermediate IPI), intermediate-risk (Deauville scores 1-3 with high-intermediate/high IPI or Deauville scores 4-5 with low/low-intermediate IPI), and high-risk (Deauville scores 4-5 and high-intermediate/high IPI). This early risk stratification showed a strong association with progression-free survival (HR, 1.00 vs. 3.98 [95% CI 2.10-7.54] vs. 13.97 [95% CI 7.02-27.83], P < 0.001). Early risk stratification using interim Deauville score and baseline IPI predicts the risk of disease progression or death in patients with DLBCL. Our results provide guidance with interim PET-driven treatment intensification strategies.
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Yang AP, Liu LG, Chen MM, Liu F, You H, Liu L, Yang H, Xun Y, Liu J, Wang RX, Brand DD, Liu D, Zheng SG, Li WX. Integrated analysis of 10 lymphoma datasets identifies E2F8 as a key regulator in Burkitt's lymphoma and mantle cell lymphoma. Am J Transl Res 2019; 11:4382-4396. [PMID: 31396343 PMCID: PMC6684893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Accepted: 06/18/2019] [Indexed: 06/10/2023]
Abstract
Burkitt's lymphoma (BURK), diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are three main types of B-cell lymphomas. This study aimed to compare the differences of affected biological functions and pathways, as well as to explore the possible regulatory mechanisms and the potential therapeutic targets in BURK, DLBCL and MCL. We performed an integrated analysis of 10 lymphoma datasets including 352 BURK patients, 880 DLBCL patients, 216 MCL patients, and 33 controls. Our results showed that signaling pathways, amino acid metabolism and several lipid metabolism pathways varies considerably among these three types of lymphoma. Furthermore, we identified several key transcription factors (TFs) and their target genes that may promote these diseases by influencing multiple carcinogenic pathways. Among these TFs, we reported first that E2F8 displayed the most significant effects in BURK and MCL. Our results demonstrate that over-expression of E2F8 activates target genes that may promote cell cycle, mitosis, immune and other cancer related functions in BURK and MCL. Therefore, we suggest that E2F8 could be used as a biomarker and potential therapeutic target for BURK and MCL. These findings would be helpful in the study of pathogenesis, and drug discovery and also in the prognosis of B cell lymphomas.
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Affiliation(s)
- An-Ping Yang
- School of Stomatology and Medicine, Foshan UniversityFoshan 528000, Guangdong, China
| | - Leyna G Liu
- Portola High School1001 Cadence, Irvine 92618, CA, USA
| | - Min-Min Chen
- School of Stomatology and Medicine, Foshan UniversityFoshan 528000, Guangdong, China
| | - Fang Liu
- School of Stomatology and Medicine, Foshan UniversityFoshan 528000, Guangdong, China
| | - Hua You
- Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityGuangzhou 510095, Guangdong, China
| | - Lian Liu
- School of Stomatology and Medicine, Foshan UniversityFoshan 528000, Guangdong, China
| | - Hua Yang
- School of Stomatology and Medicine, Foshan UniversityFoshan 528000, Guangdong, China
| | - Yang Xun
- School of Stomatology and Medicine, Foshan UniversityFoshan 528000, Guangdong, China
| | - Jing Liu
- School of Stomatology and Medicine, Foshan UniversityFoshan 528000, Guangdong, China
| | - Rui-Xue Wang
- School of Stomatology and Medicine, Foshan UniversityFoshan 528000, Guangdong, China
| | - David D Brand
- Research Service, Memphis VA Medical CenterMemphis 38104, TN, USA
| | - Dahai Liu
- School of Stomatology and Medicine, Foshan UniversityFoshan 528000, Guangdong, China
| | - Song Guo Zheng
- Department of Internal Medicine, Ohio State University College of Medicine and Wexner Medical CenterColumbus 43210, USA
| | - Wen-Xing Li
- Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of SciencesKunming 650223, Yunnan, China
- Kunming College of Life Science, University of Chinese Academy of SciencesKunming 650204, Yunnan, China
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13
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Affiliation(s)
- Christine P Lin
- Texas Tech University Health Sciences Center - School of Medicine, Lubbock, Texas
| | - Patrick M Mulvaney
- Harvard Combined Dermatology Residency Training Program, Harvard Medical School, Boston, Massachusetts
| | - Christine G Lian
- The Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Fei-Shiuann Clarissa Yang
- The Department of Dermatology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts
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14
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Aljoundi AK, Agoni C, Olotu FA, Soliman MES. Turning to Computer-aided Drug Design in the Treatment of Diffuse Large B-cell Lymphoma: Has it been Helpful? Anticancer Agents Med Chem 2019; 19:1325-1339. [PMID: 30950356 DOI: 10.2174/1871520619666190405111526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 03/18/2019] [Accepted: 03/22/2019] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Amidst the numerous effective therapeutic options available for the treatment of Diffuse Large B-cell Lymphoma (DLBCL), about 30-40% of patients treated with first-line chemoimmunotherapy still experience a relapse or refractory DLBCL. This has necessitated a continuous search for new therapeutic agents to augment the existing therapeutic arsenal. METHODS The dawn of Computer-Aided Drug Design (CADD) in the drug discovery process has accounted for persistency in the application of computational approaches either alone or in combinatorial strategies with experimental methods towards the identification of potential hit compounds with high therapeutic efficacy in abrogating DLBCL. RESULTS This review showcases the interventions of structure-based and ligand-based computational approaches which have led to the identification of numerous small molecule inhibitors against implicated targets in DLBCL therapy, even though many of these potential inhibitors are piled-up awaiting further experimental validation and exploration. CONCLUSION We conclude that a successful and a conscious amalgamation of CADD and experimental approaches could pave the way for the discovery of the next generation potential leads in DLBCL therapy with improved activities and minimal toxicities.
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Affiliation(s)
- Aimen K Aljoundi
- Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa
| | - Clement Agoni
- Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa
| | - Fisayo A Olotu
- Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa
| | - Mahmoud E S Soliman
- Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa
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15
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Jeon SY, Yhim HY, Kim HS, Kim JA, Yang DH, Kwak JY. The effect of the dexamethasone, cytarabine, and cisplatin (DHAP) regimen on stem cell mobilization and transplant outcomes of patients with non-Hodgkin's lymphoma who are candidates for up-front autologous stem cell transplantation. Korean J Intern Med 2018; 33:1169-1181. [PMID: 29295612 PMCID: PMC6234385 DOI: 10.3904/kjim.2016.163] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Accepted: 02/04/2017] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND/AIMS Data on dexamethasone, cytarabine, and cisplatin (DHAP) as a mobilization regimen, compared to high-dose cyclophosphamide (HDC), for up-front autologous stem cell transplantation (ASCT) in non-Hodgkin's lymphoma (NHL) is limited. METHODS Consecutive patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP who underwent chemomobilization using HDC or DHAP plus granulocyte-colony stimulating factor (G-CSF) for up-front ASCT were enrolled from three institutions between 2004 and 2014. RESULTS Ninety-six patients (57 men) were included. Sixty-five patients (67.7%) received HDC; and 31 (32.3%), DHAP. The total CD34+ cells mobilized were significantly higher in patients receiving DHAP (16.1 vs. 6.1 × 106/kg, p = 0.001). More patients achieved successful mobilization with DHAP (CD34+ cells ≥ 5.0 × 106/kg) compared to HDC (87.1% vs. 61.5%, respectively; p = 0.011), particularly within the first two sessions of apheresis (64.5% vs. 32.3%, respectively; p = 0.003). Mobilization failure rate (CD34+ cells < 2.0 × 106/kg) was significantly higher in patients receiving HDC (20.0% vs. 3.2%, p = 0.032). On multivariate analysis, the DHAP regimen (odds ratio, 4.12; 95% confidence interval, 1.12 to 15.17) was an independent predictor of successful mobilization. During chemomobilization, patients receiving HDC experienced more episodes of febrile neutropenia compared to patients receiving DHAP (32.3% vs. 12.9%, p = 0.043). CONCLUSION The DHAP regimen was associated with a significantly higher efficacy for stem cell mobilization and lower frequency of febrile neutropenia. Therefore, DHAP plus G-CSF is an effective for mobilization in patients with aggressive NHL who were candidates for up-front ASCT.
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Affiliation(s)
- So Yeon Jeon
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea
- Research Institute of Clinical Medicine of Chonbuk National University and Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Ho-Young Yhim
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea
- Research Institute of Clinical Medicine of Chonbuk National University and Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Hee Sun Kim
- Chonbuk National University College of Nursing, Jeonju, Korea
| | - Jeong-A Kim
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Deok-Hwan Yang
- Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Jae-Yong Kwak
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea
- Research Institute of Clinical Medicine of Chonbuk National University and Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
- Correspondence to Jae-Yong Kwak, M.D. Department of Internal Medicine, Chonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea Tel: +82-63-250-1791 Fax: +82-63-254-1609 E-mail:
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16
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Liu Z, Meng J, Li X, Zhu F, Liu T, Wu G, Zhang L. Identification of Hub Genes and Key Pathways Associated with Two Subtypes of Diffuse Large B-Cell Lymphoma Based on Gene Expression Profiling via Integrated Bioinformatics. BIOMED RESEARCH INTERNATIONAL 2018; 2018:3574534. [PMID: 29992138 PMCID: PMC5994323 DOI: 10.1155/2018/3574534] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 03/27/2018] [Accepted: 04/04/2018] [Indexed: 12/12/2022]
Abstract
There is a significant difference in prognosis between the germinal center B-cell (GCB) and activated B-cell (ABC) subtypes of diffuse large B-cell lymphoma (DLBCL). However, the signaling pathways and driver genes involved in these disparate subtypes are ambiguous. This study integrated three cohort profile datasets, including 250 GCB samples and 250 ABC samples, to elucidate potential candidate hub genes and key pathways involved in these two subtypes. Differentially expressed genes (DEGs) were identified. After Gene Ontology functional enrichment analysis of the DEGs, protein-protein interaction (PPI) network and sub-PPI network analyses were conducted using the STRING database and Cytoscape software. Subsequently, the Oncomine database and the cBioportal online tool were employed to verify the alterations and differential expression of the 8 hub genes (MME, CD44, IRF4, STAT3, IL2RA, ETV6, CCND2, and CFLAR). Gene set enrichment analysis was also employed to identify the intersection of the key pathways (JAK-STAT, FOXO, and NF-κB pathways) validated in the above analyses. These hub genes and key pathways could improve our understanding of the process of tumorigenesis and the underlying molecular events and may be therapeutic targets for the precise treatment of these two subtypes with different prognoses.
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Affiliation(s)
- Zijian Liu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jingshu Meng
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoqian Li
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fang Zhu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Liu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Gang Wu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liling Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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17
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Yhim HY, Kim JA, Ko SH, Park Y, Yim E, Kim HS, Kwak JY. The prognostic significance of CD11b +CX3CR1 + monocytes in patients with newly diagnosed diffuse large B-cell lymphoma. Oncotarget 2017; 8:92289-92299. [PMID: 29190915 PMCID: PMC5696181 DOI: 10.18632/oncotarget.21241] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Accepted: 08/17/2017] [Indexed: 12/14/2022] Open
Abstract
Despite their critical roles in angiogenesis and host immunosuppression within the tumor microenvironment, the prognostic significance of myeloid-lineage cells expressing CD11b and CX3CR1 in diffuse large B-cell lymphoma (DLBCL) has not been well studied. We prospectively enrolled newly-diagnosed DLBCL patients at two Korean institutions between May 2011 and Aug 2015. CD11b+CX3CR1+ cells were analyzed by flow cytometry using peripheral blood (PB) and bone marrow (BM) aspirate samples before treatments. Eighty-nine patients (52 males) were enrolled. The median age was 65 years (range, 19–88 years). Thirty-seven patients (42%) were classified as high-intermediate or high risk according to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI). Patients were categorized into either high or low PB-/BM-CD11b+CX3CR1+ monocyte group according to the cutoffs identified by the receiver-operating-characteristics analysis (PB, 3.68%; BM, 3.45%). The high PB-CD11b+CX3CR1+ monocyte group was significantly associated with high-intermediate and high risk NCCN-IPI group (P = 0.004). With a median follow-up of 27.7 months (range, 1.7-60.4 months), the low PB-CD11b+CX3CR1+ monocyte group showed significantly better overall survival (OS) than the high PB-CD11b+CX3CR1+ monocyte group (3-year, 92.3% vs. 51.2%, respectively; P < 0.001). In contrast, no significant difference was observed between the high and low BM-CD11b+CX3CR1+ monocyte groups. Among patients with high-intermediate to high risk NCCN-IPI, the high PB-CD11b+CX3CR1+ monocyte group showed significantly worse OS than the low PB-CD11b+CX3CR1+ monocyte group (3-year, 29.3% vs. 80.2%, respectively; P = 0.008). Taken together, PB-CD11b+CX3CR1+ monocyte percentage correlates with the NCCN-IPI risk stratification, which enables identification of subgroups with extremely poor clinical outcomes.
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Affiliation(s)
- Ho-Young Yhim
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.,Research Institute of Clinical Medicine, Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea
| | - Jeong-A Kim
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.,Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sun-Hye Ko
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Youngrok Park
- Tumor Biology Training Program, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, USA
| | - Eunjung Yim
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hee Sun Kim
- College of Nursing, Chonbuk National University, Jeonju, Republic of Korea
| | - Jae-Yong Kwak
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea
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18
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Lee H, Kim YR, Kim SJ, Park Y, Eom HS, Oh SY, Kim HJ, Kang HJ, Lee WS, Moon JH, Won YW, Kim TS, Kim JS. Clinical outcomes in patients with diffuse large B cell lymphoma with a partial response to first-line R-CHOP chemotherapy: prognostic value of secondary International Prognostic Index scores and Deauville scores. Ann Hematol 2017; 96:1873-1881. [PMID: 28831584 DOI: 10.1007/s00277-017-3107-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Accepted: 08/16/2017] [Indexed: 12/21/2022]
Abstract
After introducing a rituximab-containing chemoimmunotherapy (R-CHOP) for diffuse large B cell lymphoma (DLBCL), a partial response (PR) which is regarded as treatment failure is still observed. To investigate the prognostic factors for the DLBCL patients with a PR to R-CHOP, we retrospectively evaluated 758 newly diagnosed DLBCL patients. After R-CHOP, 88 (11.6%) achieved a PR. Three-year progression-free and overall survival rates measured from the date of PR achievement (PFS2 and OS2) were 57.4 and 67.8%, respectively. The secondary International Prognostic Index (IPI2) scores after R-CHOP were low (0-1) in 68.2% and high (2-3) in 31.8% of the patients. The Deauville scores from 18-fluorodeoxyglucose positron emission tomography after R-CHOP showed low (2-3) in 58.0% and high (4) in 42.0% of the patients. High IPI2 and high Deauville scores were associated with worse PFS2 (P < 0.001 and P = 0.009) and OS2 (P = 0.013 and P = 0.067). The high-risk group defined by the IPI2 and Deauville scores, whose scores were both high, showed significantly lower 3-year PFS2 (P < 0.001) and OS2 (P = 0.006) rates compared with those of the other groups. In multivariate analyses, the IPI score of ≥ 3 at diagnosis and bone marrow involvement at diagnosis were independent prognostic factors. In addition, high IPI2-Deauville score after R-CHOP was significantly associated with poor PFS2 (P = 0.009) and demonstrated a trend toward inferior OS2. In conclusion, DLBCL patients who partially responded to R-CHOP are still a heterogeneous group, for which IPI2 and Deauville scores should be evaluated for prediction of prognosis.
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Affiliation(s)
- Hyewon Lee
- Center for Hematologic Malignancy, National Cancer Center, Goyang, South Korea
| | - Yu Ri Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea
| | - Soo-Jeong Kim
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea
| | - Yong Park
- Division of Hematology-Oncology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Hyeon-Seok Eom
- Center for Hematologic Malignancy, National Cancer Center, Goyang, South Korea
| | - Sung Yong Oh
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea
| | - Hyo Jung Kim
- Division of Hematology-Oncology, Department of Internal Medicine, College of Medicine, Hallym University, Hallym University Sacred Heart Hospital, Anyang, South Korea
| | - Hye Jin Kang
- Division of Hematology-Oncology, Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea
| | - Won-Sik Lee
- Division of Hematology-Oncology, Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea
| | - Joon Ho Moon
- Department of Hematology and Medical Oncology, Kyungpook National University Hospital, Daegu, South Korea
| | - Young-Woong Won
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea
| | - Tae-Sung Kim
- Department of Nuclear Medicine, National Cancer Center, Goyang, South Korea
| | - Jin Seok Kim
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
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19
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Ravindra VM, Raheja A, Corn H, Driscoll M, Welt C, Simmons DL, Couldwell WT. Primary pituitary diffuse large B-cell lymphoma with somatotroph hyperplasia and acromegaly: case report. J Neurosurg 2016; 126:1725-1730. [PMID: 27518527 DOI: 10.3171/2016.5.jns16828] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and comprises approximately 30% of all lymphomas. Patients typically present with a nonpainful mass in the neck, groin, or abdomen associated with constitutional symptoms. In this report, however, the authors describe a rare case of a 61-year-old woman with hyperprolactinemia, hypothyroidism, and acromegaly (elevation of insulin-like growth factor-1 [IGF-1]) with elevated growth hormone-releasing hormone (GHRH) in whom an MRI demonstrated diffuse enlargement of the pituitary gland. Despite medical treatment, the patient had persistent elevation of IGF-1. She underwent a transsphenoidal biopsy, which yielded a diagnosis of DLBCL with an activated B-cell immunophenotype with somatotroph hyperplasia. After stereo-tactic radiation therapy in combination with chemotherapy, she is currently in remission from her lymphoma and has normalized IGF-1 levels without medical therapy, 8 months after her histopathological diagnosis. This is the only reported case of its kind and displays the importance of a broad differential diagnosis, multidisciplinary evaluation, and critical intraoperative decision-making when treating atypical sellar lesions.
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Affiliation(s)
- Vijay M Ravindra
- Department of Neurosurgery, Clinical Neurosciences Center and Huntsman Cancer Institute
| | - Amol Raheja
- Department of Neurosurgery, Clinical Neurosciences Center and Huntsman Cancer Institute
| | - Heather Corn
- Department of Internal Medicine, Division of Endocrinology, and
| | - Meghan Driscoll
- Department of Pathology, University of Utah, Salt Lake City, Utah
| | - Corrine Welt
- Department of Internal Medicine, Division of Endocrinology, and
| | - Debra L Simmons
- Department of Internal Medicine, Division of Endocrinology, and
| | - William T Couldwell
- Department of Neurosurgery, Clinical Neurosciences Center and Huntsman Cancer Institute
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20
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Choi YW, Ahn MS, Choi JH, Lee HW, Kang SY, Jeong SH, Park JS, Han JH, Kim JH, Sheen SS. High expression of Bcl-2 predicts poor outcome in diffuse large B-cell lymphoma patients with low international prognostic index receiving R-CHOP chemotherapy. Int J Hematol 2015; 103:210-8. [PMID: 26586460 DOI: 10.1007/s12185-015-1911-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 11/11/2015] [Accepted: 11/12/2015] [Indexed: 11/24/2022]
Abstract
The prognostic significance of Bcl-2, Bcl-6, p53, topoisomerase II, and β-tubulin expression was evaluated in diffuse large B-cell lymphoma (DLBCL) patients treated with cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab. Eight-year progression-free survival (PFS, P = 0.006) and overall survival (OS, P = 0.001) of patients with high Bcl-2 expression were significantly inferior to those of patients with low expression without prognostic significance of Bcl-6, p53, topoisomerase II, and β-tubulin expression. High expression of Bcl-2 was associated with poor PFS (P = 0.045) and OS (P = 0.004) only in patients with low international prognostic index (IPI). In multivariate analysis, high expression of Bcl-2 was a significant independent prognostic factor of poor PFS (P = 0.026) and OS (P = 0.007) along with high IPI. In conclusion, the expression of Bcl-2 may be a useful prognostic factor, especially in DLBCL patients with low IPI.
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Affiliation(s)
- Yong Won Choi
- Department of Hematology-Oncology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon, 16499, Republic of Korea
| | - Mi Sun Ahn
- Department of Hematology-Oncology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon, 16499, Republic of Korea
| | - Jin-Hyuk Choi
- Department of Hematology-Oncology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon, 16499, Republic of Korea
| | - Hyun Woo Lee
- Department of Hematology-Oncology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon, 16499, Republic of Korea.
| | - Seok Yun Kang
- Department of Hematology-Oncology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon, 16499, Republic of Korea
| | - Seong Hyun Jeong
- Department of Hematology-Oncology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon, 16499, Republic of Korea
| | - Joon Seong Park
- Department of Hematology-Oncology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon, 16499, Republic of Korea
| | - Jae Ho Han
- Department of Pathology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon, 16499, Republic of Korea.
| | - Jang-Hee Kim
- Department of Pathology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon, 16499, Republic of Korea
| | - Seung Soo Sheen
- Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Republic of Korea
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21
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Shin HC, Seo J, Kang BW, Moon JH, Chae YS, Lee SJ, Lee YJ, Han S, Seo SK, Kim JG, Sohn SK, Park TI. Clinical significance of nuclear factor κB and chemokine receptor CXCR4 expression in patients with diffuse large B-cell lymphoma who received rituximab-based therapy. Korean J Intern Med 2014; 29:785-92. [PMID: 25378977 PMCID: PMC4219968 DOI: 10.3904/kjim.2014.29.6.785] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2013] [Revised: 08/20/2013] [Accepted: 01/06/2014] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND/AIMS This study investigated the expression of nuclear factor κB (NF-κB) and the chemokine receptor (CXCR4) in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. METHODS Seventy patients with DLBCL and treated with rituximab-CHOP (R-CHOP) were included, and immunohistochemistry was performed to determine the expression of NF-κB (IκB kinase α, p50, and p100/p52) and CXCR4. To classify DLBCL cases as germinal center B-cell-like (GCB) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 was used in this study. The expression was divided into two groups according to the intensity score (negative, 0 or 1+; positive, 2+ or 3+). RESULTS The median age of the patients was 66 years (range, 17 to 87), and 58.6% were male. Twenty-seven patients (38.6%) had stage III or IV disease at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their International Prognostic Indexs (IPIs). The overall incidence of bone marrow involvement was 5.7%. Rates of positive NF-κB and CXCR4 expression were 84.2% and 88.6%, respectively. High NF-κB expression was associated with CXCR4 expression (p = 0.002), and 56 patients (80.0%) showed coexpression. However, the expression of NF-κB or CXCR4 was not associated with overall survival and EFS. On multivariate analysis that included age, gender, performance status, stage, and the IPI, no significant association between the grade of NF-κB or CXCR4 expression and survival was observed. CONCLUSIONS The current study suggests that the tissue expression of NF-κB and CXCR4 may not be an independent prognostic marker in DLBCL patients treated with R-CHOP.
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MESH Headings
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal, Murine-Derived/administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Biomarkers, Tumor/analysis
- Chi-Square Distribution
- Cyclophosphamide/administration & dosage
- Disease Progression
- Disease-Free Survival
- Doxorubicin/administration & dosage
- Female
- Humans
- Immunohistochemistry
- Kaplan-Meier Estimate
- Lymphoma, Large B-Cell, Diffuse/chemistry
- Lymphoma, Large B-Cell, Diffuse/drug therapy
- Lymphoma, Large B-Cell, Diffuse/mortality
- Lymphoma, Large B-Cell, Diffuse/pathology
- Male
- Middle Aged
- Multivariate Analysis
- NF-kappa B/analysis
- Neoplasm Staging
- Predictive Value of Tests
- Prednisone/administration & dosage
- Proportional Hazards Models
- Receptors, CXCR4/analysis
- Retrospective Studies
- Risk Factors
- Rituximab
- Time Factors
- Treatment Outcome
- Vincristine/administration & dosage
- Young Adult
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Affiliation(s)
- Ho Cheol Shin
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Jongwon Seo
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Byung Woog Kang
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Joon Ho Moon
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Yee Soo Chae
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Soo Jung Lee
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Yoo Jin Lee
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Seoae Han
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Sang Kyung Seo
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Jong Gwang Kim
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Sang Kyun Sohn
- Department of Hematology and Oncology, Kyungpook National University Hospital, Daegu, Korea
| | - Tae-In Park
- Department of Pathology, Kyungpook National University Hospital, Daegu, Korea
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