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Cheng B, Zhang H, Qi C, Zhu G, Huang L, Wang X. Extramedullary relapsed acute lymphoblastic leukemia presenting as asymptomatic acute kidney injury after hematopoietic stem cell transplantation. Pediatr Nephrol 2024; 39:1779-1781. [PMID: 38030834 DOI: 10.1007/s00467-023-06229-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 11/03/2023] [Accepted: 11/05/2023] [Indexed: 12/01/2023]
Abstract
Acute kidney injury (AKI) is a common complication in children with hematological malignancies. Although AKI due to infiltration of tumor cells in children is rare, it negatively impacts treatment outcomes and increases the risk of mortality. We introduce a case of a child with acute lymphoblastic leukemia (ALL) who experienced kidney relapse resulting in asymptomatic AKI after remission from treatment, to remind clinicians not to overlook the primary disease in clinical judgment. In cases of unexplained AKI, kidney biopsy should be performed when feasible to get an accurate diagnosis and scientific treatment. In brief, children with leukemia who have achieved remission after treatment still need regular monitoring of urine routine and kidney function.
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Affiliation(s)
- Bingjie Cheng
- Department of Nephrology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongying Zhang
- Department of Nephrology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chang Qi
- Department of Nephrology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Gaohong Zhu
- Department of Nephrology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lin Huang
- Department of Nephrology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaowen Wang
- Department of Nephrology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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2
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Arias-Espinosa L, Acosta-Medina AA, Vargas-España A, Fuentes-Martin V, Colunga-Pedraza PR, Hawing-Zarate JA, Leon AGD, Soto-Mota A, Pacheco-Gutierrez G, Vargas-Serafín C, Barrera-Lumbreras G, Bourlon C. Acute Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The Good, the Bad, and the Ugly of Isolated Extramedullary Relapse in a Latin American Population. Transplant Cell Ther 2023; 29:510.e1-510.e9. [PMID: 37169289 DOI: 10.1016/j.jtct.2023.05.006] [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: 02/07/2023] [Revised: 04/14/2023] [Accepted: 05/04/2023] [Indexed: 05/13/2023]
Abstract
Hematopoietic stem cell transplantation (HSCT) is an effective therapy for acute leukemia (AL). Relapse represents the main cause of mortality. Isolated extramedullary relapse (iEMR) is atypical and has been related to better outcomes. Here we describe the clinical characteristics and outcomes of AL relapse after HSCT in our study population and analyze the impacts of different types of relapse on survival outcomes. This retrospective, multicenter study included 124 patients age ≥15 years with AL who underwent HSCT between 2004 and 2019. At diagnosis, 66.1% of the patients had lymphocytic AL, 19.7% presented with high-risk features, and 18.5% had extramedullary disease (EMD). At HSCT, 83.1% of the patients were in complete remission (CR), and 44.8% had negative measurable residual disease (MRD). The vast majority of donors were related (96%), including 48.4% HLA-matched and 47.6% haploidentical. Myeloablative conditioning was provided to 80.6% of patients. The median overall survival (OS) was 15 months (95% confidence interval [CI] 9.9 to 20.1 months). Factors associated with improved OS were adolescent and young adult (AYA) patient (P = .035), first or second CR (P = .026), and chronic graft-versus-host disease (GVHD) (P < .001). Acute GVHD grade III-IV (P = .009) was associated with increased mortality. The median relapse-free survival was 13 months (95% CI, 7.17 to 18.8 months); early disease status (P = .017) and chronic GVHD (P < .001) had protective roles. Sixty-eight patients (55%) relapsed after HSCT, with a median time to relapse of 6 months (95% CI, 3.6 to 8.4 months). iEMR was reported in 16 patients (23.5%). The most commonly involved extramedullary sites were the central nervous system and skin. Compared to patients with bone marrow relapse, all patients with iEMR had a diagnosis of acute lymphoid leukemia (P = .008), and 93.8% belonged to the AYA group; regarding pre-HSCT characteristics, iEMR patients had higher rates of negative MRD (P = .06) and a history of EMD (P = .009). Seventy-seven percent of relapsed patients received additional treatment with curative intent. The median OS after relapse (OSr) was 4 months (95% CI, 2.6 to 5.4 months). Factors related to increased OSr included lymphoid phenotype (P = .03), iEMR (P = .0042), late relapse (≥6 months) (P = .014), receipt of systemic therapy including second HSCT (P < .001), and response to therapy (P < .001). Rates of relapse and iEMR were higher than those previously reported in other studies. Advanced disease, reduced-intensity conditioning, and a diminished graft-versus-leukemia effect were factors influencing these findings. At relapse, presenting with iEMR after 6 months and receiving intensive therapy with adequate response were associated with better outcomes. Our results strongly suggest that a personalized approach to treating patients with HSCT is needed to counterbalance specific adverse factors and can positively impact clinical outcomes.
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Affiliation(s)
- Luis Arias-Espinosa
- Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Aldo A Acosta-Medina
- Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Andres Vargas-España
- Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Valerie Fuentes-Martin
- Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Perla R Colunga-Pedraza
- Department of Hematology, Universidad Autonoma de Nuevo Leon, Facultad de Medicina y Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, Mexico
| | - Jose Angel Hawing-Zarate
- Department of Hematology, Universidad Autonoma de Nuevo Leon, Facultad de Medicina y Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, Mexico
| | - Andres Gómez-De Leon
- Department of Hematology, Universidad Autonoma de Nuevo Leon, Facultad de Medicina y Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, Mexico
| | - Adrian Soto-Mota
- Metabolic Diseases Research Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; School of Medical Sciences, Monterrey Institute of Technology and Higher Education, Mexico City, Mexico
| | - Guillermo Pacheco-Gutierrez
- Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Cesar Vargas-Serafín
- Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Georgina Barrera-Lumbreras
- Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Christianne Bourlon
- Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.
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Fraccaroli A, Vogt D, Rothmayer M, Spiekermann K, Pastore F, Tischer J. Impact of extramedullary disease in AML patients undergoing sequential RIC for HLA-matched transplantation: occurrence, risk factors, relapse patterns, and outcome. Ann Hematol 2023:10.1007/s00277-023-05281-8. [PMID: 37300568 DOI: 10.1007/s00277-023-05281-8] [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: 05/23/2022] [Accepted: 05/14/2023] [Indexed: 06/12/2023]
Abstract
We sought to evaluate the role of extramedullary disease (EMD) in sequential RIC retrospectively analyzing data of 144 high-risk AML patients undergoing HLA-matched transplantation. Median long-term follow-up was 11.6 years. Eighteen percent of patients (n = 26/144) presented with extramedullary AML (EM AML) or a history of EMD at time of transplantation. Overall relapse rate was 25% (n = 36/144) with 15% (n = 21/144) of all patients developing isolated BM relapse and 10% (n = 15/144) developing EM AML relapse with or without concomitant BM relapse (EM ± BM). Manifestation of EM relapse after transplantation occurred frequently at multiple sites and presented mostly as solid tumor mass. Only 3/15 patients with EM ± BM relapse showed a prior EMD manifestation. EMD prior to allogeneic transplantation had no impact on post-transplant OS when compared to non-EMD (median post-transplant OS 3.8 years versus 4.8 years; ns). Risk factors (p = < 0.1) for EM ± BM relapse included younger age and a higher number of prior intensive chemotherapies, whereas the presence of chronic GVHD was a protective factor. Median post-transplant OS (15.5 months vs. 15.5 months), RFS (9.6 months vs 7.3 months), and post-relapse OS (6.7 months vs. 6.3 months) were not significantly different between patients with isolated BM vs. EM ± BM relapse. Taken together, occurrence of EMD prior to as well as of EM ± BM AML relapse after transplantation was moderate, presenting mostly as solid tumor mass after transplantation. However, diagnosis of those does not seem to influence outcomes after sequential RIC. A higher number of chemotherapy cycles prior to transplantation was identified as recent risk factor for EM ± BM relapse.
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Affiliation(s)
- Alessia Fraccaroli
- Department of Internal Medicine III, University Hospital Munich, Ludwig-Maximilian-University (LMU), Munich, Germany
| | - Daniela Vogt
- Department of Internal Medicine III, University Hospital Munich, Ludwig-Maximilian-University (LMU), Munich, Germany
| | - Margarete Rothmayer
- Department of Internal Medicine III, University Hospital Munich, Ludwig-Maximilian-University (LMU), Munich, Germany
| | - Karsten Spiekermann
- Department of Internal Medicine III, University Hospital Munich, Ludwig-Maximilian-University (LMU), Munich, Germany
| | - Friederike Pastore
- Department of Internal Medicine III, University Hospital Munich, Ludwig-Maximilian-University (LMU), Munich, Germany.
| | - Johanna Tischer
- Department of Internal Medicine III, University Hospital Munich, Ludwig-Maximilian-University (LMU), Munich, Germany
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Yuan J, Wang F, Ren H. Intrathecal CAR-NK cells infusion for isolated CNS relapse after allogeneic stem cell transplantation: case report. Stem Cell Res Ther 2023; 14:44. [PMID: 36941630 PMCID: PMC10029298 DOI: 10.1186/s13287-023-03272-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 03/08/2023] [Indexed: 03/23/2023] Open
Abstract
A 24-year-old man with central nervous system (CNS) involvement of T-cell lineage acute lymphoblastic leukemia received sibling allogeneic stem cell transplantation (allo-SCT). He developed isolated CNS relapse early post-SCT, while high-dose systemic chemotherapy, intrathecal (IT) triple infusion and IT donor lymphocytes infusion (DLI) all demonstrated effectiveness. We performed IT umbilical cord blood-derived CAR-NK (target CD7) cells infusion, which was not previously reported. After infusion, detection of cytokines revealed that interferon-γ, interleukin-6 and interleukin-8 increased in CSF. He developed high fever, headache, nausea, vomiting and a spinal cord transection with incontinence in a short time, whereas the ptosis and blurred vision improved completely. The bone marrow remained encouragingly complete remission and complete donor chimerism over 9 months after IT CAR-NK cells infusion. In conclusion, IT CAR-NK cells infusion is a potentially feasible and effective option for patients with CNS relapse, with limited neurological toxicity.
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Affiliation(s)
- Jing Yuan
- Department of Hematology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000, Hebei, China.
| | - Fuxu Wang
- Department of Hematology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000, Hebei, China.
| | - Hanyun Ren
- Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
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Li DP, Liu CZ, Jeremy M, Li X, Wang JC, Nath Varma S, Gai TT, Tian WQ, Zou Q, Wei YM, Wang HY, Long CJ, Zhou Y. Myeloid sarcoma with ulnar nerve entrapment: A case report. World J Clin Cases 2022; 10:10227-10235. [PMID: 36246824 PMCID: PMC9561602 DOI: 10.12998/wjcc.v10.i28.10227] [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: 04/28/2022] [Revised: 06/25/2022] [Accepted: 08/23/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Myeloid sarcoma (MS) is relatively rare, occurring mainly in the skin and lymph nodes, and MS invasion of the ulnar nerve is particularly unusual. The main aim of this article is to present a case of MS invading the brachial plexus, causing ulnar nerve entrapment syndrome, and to further clinical understanding of the possibility of MS invasion of peripheral nerves.
CASE SUMMARY We present the case of a 46-year-old man with a 13-year history of well-treated acute nonlymphocytic leukaemia who was admitted to the hospital after presenting with numbness and pain in his left little finger. The initial diagnosis was considered a simple case of nerve entrapment disease, with magnetic resonance imaging showing slightly abnormal left brachial plexus nerve alignment with local thickening, entrapment, and high signal on compression lipid images. Due to the severity of the ulnar nerve compression, we surgically investigated and cleared the entrapment and nerve tissue hyperplasia; however, subsequent pathological biopsy results revealed evidence of MS. The patient had significant relief from his neurological symptoms, with no postoperative complications, and was referred to the haemato-oncology department for further consultation about the primary disease. This is the first report of safe treatment of ulnar nerve entrapment from MS. It is intended to inform hand surgeons that nerve entrapment may be associated with extramedullary MS, as a rare presenting feature of the disease.
CONCLUSION MS invasion of the brachial plexus and surrounding tissues of the upper arm, resulting in ulnar nerve entrapment and degeneration with significant neurological pain and numbness in the little finger, is uncommon. Surgical treatment significantly relieved the patient’s nerve entrapment symptoms and prevented further neurological impairment. This case is reported to highlight the rare presenting features of MS.
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Affiliation(s)
- Da-Peng Li
- Yantai Hospital of Shandong Wendeng Osteopathic & Traumatology, Hand and Foot Microsurgery, Yantai 264009, Shandong Province, China
| | - Chao-Zong Liu
- University College London, Royal National Orthopaedic Hospital, London HA7 4LP, United Kingdom
| | - Mortimer Jeremy
- University College London, Royal National Orthopaedic Hospital, London HA7 4LP, United Kingdom
| | - Xin Li
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130000, Jilin Province, China
| | - Jin-Chao Wang
- Yantai Hospital of Shandong Wendeng Osteopathic & Traumatology, Hand and Foot Microsurgery, Yantai 264009, Shandong Province, China
| | - Swastina Nath Varma
- University College London, Royal National Orthopaedic Hospital, London HA7 4LP, United Kingdom
| | - Ting-Ting Gai
- Yantai Hospital of Shandong Wendeng Osteopathic & Traumatology, Hand and Foot Microsurgery, Yantai 264009, Shandong Province, China
| | - Wei-Qi Tian
- Yantai Hospital of Shandong Wendeng Osteopathic & Traumatology, Hand and Foot Microsurgery, Yantai 264009, Shandong Province, China
| | - Qi Zou
- Yantai Hospital of Shandong Wendeng Osteopathic & Traumatology, Hand and Foot Microsurgery, Yantai 264009, China
| | - Yan-Mian Wei
- Yantai Hospital of Shandong Wendeng Osteopathic & Traumatology, Hand and Foot Microsurgery, Yantai 264009, Shandong Province, China
| | - Hao-Yu Wang
- University College London, Royal National Orthopaedic Hospital, London HA7 4LP, United Kingdom
| | - Chang-Jiang Long
- Qinhai University, Medical Institute, Xining 810000, Qinhai Province, China
| | - Yu Zhou
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130000, Jilin Province, China
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Leotta S, Condorelli A, Sciortino R, Milone GA, Bellofiore C, Garibaldi B, Schininà G, Spadaro A, Cupri A, Milone G. Prevention and Treatment of Acute Myeloid Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The State of the Art and Future Perspectives. J Clin Med 2022; 11:253. [PMID: 35011994 PMCID: PMC8745746 DOI: 10.3390/jcm11010253] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 12/24/2021] [Accepted: 12/28/2021] [Indexed: 12/19/2022] Open
Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) for high-risk acute myeloid leukemia (AML) represents the only curative option. Progress has been made in the last two decades in the pre-transplant induction therapies, supportive care, selection of donors and conditioning regimens that allowed to extend the HSCT to a larger number of patients, including those aged over 65 years and/or lacking an HLA-identical donor. Furthermore, improvements in the prophylaxis of the graft-versus-host disease and of infection have dramatically reduced transplant-related mortality. The relapse of AML remains the major reason for transplant failure affecting almost 40-50% of the patients. From 10 to 15 years ago to date, treatment options for AML relapsing after HSCT were limited to conventional cytotoxic chemotherapy and donor leukocyte infusions (DLI). Nowadays, novel agents and targeted therapies have enriched the therapeutic landscape. Moreover, very recently, the therapeutic landscape has been enriched by manipulated cellular products (CAR-T, CAR-CIK, CAR-NK). In light of these new perspectives, careful monitoring of minimal-residual disease (MRD) and prompt application of pre-emptive strategies in the post-transplant setting have become imperative. Herein, we review the current state of the art on monitoring, prevention and treatment of relapse of AML after HSCT with particular attention on novel agents and future directions.
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Affiliation(s)
| | - Annalisa Condorelli
- Division of Hematology, AOU “Policlinico G. Rodolico-San Marco”, Via Santa Sofia 78, 95124 Catania, Italy; (S.L.); (R.S.); (G.A.M.); (C.B.); (B.G.); (G.S.); (A.S.); (A.C.); (G.M.)
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Sheikh IN, Ragoonanan D, Franklin A, Srinivasan C, Zhao B, Petropoulos D, Mahadeo KM, Tewari P, Khazal SJ. Cardiac Relapse of Acute Lymphoblastic Leukemia Following Hematopoietic Stem Cell Transplantation: A Case Report and Review of Literature. Cancers (Basel) 2021; 13:5814. [PMID: 34830969 PMCID: PMC8616080 DOI: 10.3390/cancers13225814] [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: 10/14/2021] [Revised: 11/13/2021] [Accepted: 11/17/2021] [Indexed: 12/23/2022] Open
Abstract
Isolated extramedullary relapse of acute lymphoblastic leukemia (ALL) occurs in soft tissues and various organs outside the testis and central nervous system. Treatments such as hematopoietic stem cell transplantation and more novel modalities such as immunotherapy have eradicated ALL at extramedullary sites. In some instances, survival times for relapsed ALL at these sites are longer than those for relapsed disease involving only the bone marrow. Isolated relapse of ALL in the myocardium is rare, especially in children, making diagnosis and treatment of it difficult. More recent treatment options such as chimeric antigen receptor T-cell therapy carry a high risk of cytokine release syndrome and associated risk of worsening cardiac function. Herein we present the case of an 11-year-old boy who presented with relapsed symptomatic B-cell ALL in the myocardium following allogeneic hematopoietic stem cell transplantation. This is an unusual presentation of relapsed ALL and this case demonstrates the associated challenges in its diagnosis and treatment. The case report is followed by a literature review of the advances in treatment of pediatric leukemia and their application to extramedullary relapse of this disease in particular.
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Affiliation(s)
- Irtiza N. Sheikh
- Division of Pediatrics and Patient Care, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Dristhi Ragoonanan
- Department of Pediatrics, Pediatric Stem Cell Transplantation and Cellular Therapy, CARTOX Program, University of Texas at MD Anderson Cancer Center, Houston, TX 77030, USA; (D.R.); (D.P.); (K.M.M.); (P.T.)
| | - Anna Franklin
- Center for Cancer and Blood Disorders, Children’s Hospital Colorado, Aurora, CO 80045, USA;
| | - Chandra Srinivasan
- Cardiac Center, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA;
| | - Bhiong Zhao
- Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center McGovern Medical School, Houston, TX 77054, USA;
| | - Demetrios Petropoulos
- Department of Pediatrics, Pediatric Stem Cell Transplantation and Cellular Therapy, CARTOX Program, University of Texas at MD Anderson Cancer Center, Houston, TX 77030, USA; (D.R.); (D.P.); (K.M.M.); (P.T.)
| | - Kris M. Mahadeo
- Department of Pediatrics, Pediatric Stem Cell Transplantation and Cellular Therapy, CARTOX Program, University of Texas at MD Anderson Cancer Center, Houston, TX 77030, USA; (D.R.); (D.P.); (K.M.M.); (P.T.)
| | - Priti Tewari
- Department of Pediatrics, Pediatric Stem Cell Transplantation and Cellular Therapy, CARTOX Program, University of Texas at MD Anderson Cancer Center, Houston, TX 77030, USA; (D.R.); (D.P.); (K.M.M.); (P.T.)
| | - Sajad J. Khazal
- Department of Pediatrics, Pediatric Stem Cell Transplantation and Cellular Therapy, CARTOX Program, University of Texas at MD Anderson Cancer Center, Houston, TX 77030, USA; (D.R.); (D.P.); (K.M.M.); (P.T.)
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8
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Different Kinetics and Risk Factors for Isolated Extramedullary Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Leukemia. Transplant Cell Ther 2021; 27:859.e1-859.e10. [PMID: 34216791 DOI: 10.1016/j.jtct.2021.06.023] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 06/15/2021] [Accepted: 06/20/2021] [Indexed: 12/18/2022]
Abstract
Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of post-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR compared with systemic relapse. The 5-year cumulative incidence of systemic relapse (either bone marrow [BM] only or BM combined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; P = .013). Complete response (CR) 2+/active disease at transplantation (hazard ratio [HR], 3.1; P < .001) and prior EM disease (HR, 2.3; P = .007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5; P = .043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% versus 15.3%; P = .089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, whereas those experiencing their iEMR at first relapse developed further systemic relapse and iEMR at approximately similar frequencies. A second iEMR was more common after a first iEMR than after a first systemic relapse (58.8% versus 13.0%; P = .001) and was associated with poor outcome. iEMR has a poor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes.
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9
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Prognosis and risk factors for central nervous system relapse after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Ann Hematol 2021; 100:505-516. [PMID: 33389025 DOI: 10.1007/s00277-020-04380-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 12/16/2020] [Indexed: 12/17/2022]
Abstract
We performed a nested case-control study to investigate the incidence, treatment, and prognosis of central nervous system (CNS) relapse after allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) and compared the outcomes of patients with CNS relapse following haploidentical donor (HID) HSCT versus identical sibling donor (ISD) HSCT. A total of 37 patients (HID-HSCT, 24; ISD-HSCT, 13) developed CNS relapse after transplantation between January 2009 and January 2019, with an incidence of 1.81%. The median time from transplantation to CNS relapse was 239 days. Pre-HSCT CNS involvement (HR 6.940, 95% CI 3.146-15.306, p < .001) was an independent risk factor for CNS relapse after allo-HSCT for AML. The 3-year overall survival (OS) for patients with CNS relapse was 60.3 ± 8.8%, which was significantly lower than that in the controls (81.5 ± 4.5%, p = .003). The incidence of CNS relapse was 1.64% for patients who received HID-HSCT and 2.55% for those who received ISD-HSCT (p = .193). There was no significant difference in OS between the HID-HSCT and ISD-HSCT subgroups among the patients with CNS relapse. In conclusion, CNS relapse is a rare but serious complication after allo-HSCT for AML, and the incidence and outcomes of patients with CNS relapse are comparable following HID-HSCT and ISD-HSCT.
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10
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Shallis RM, Gale RP, Lazarus HM, Roberts KB, Xu ML, Seropian SE, Gore SD, Podoltsev NA. Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved. Blood Rev 2020; 47:100773. [PMID: 33213985 DOI: 10.1016/j.blre.2020.100773] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 09/01/2020] [Accepted: 10/02/2020] [Indexed: 02/06/2023]
Abstract
The World Health Organization classification and definition of "myeloid sarcoma" is imprecise and misleading. A more accurate term is "extramedullary acute myeloid leukemia tumor (eAML)." The pathogenesis of eAML has been associated with aberrancy of cellular adhesion molecules, chemokine receptors/ligands and RAS-MAPK/ERK signaling. eAML can present with or without synchronous or metachronous intramedullary acute myeloid leukemia (AML) so a bone marrow evaluation is always recommended. Accurate diagnosis of eAML requires tissue biopsy. eAML confined to one or a few sites is frequently treated with local therapy such as radiotherapy. About 75-90% of patients with isolated eAML will develop metachronous intramedullary AML with a median latency period ranging from 4 to 12 months; thus, patients with isolated eAML may also be treated with systemic anti-leukemia therapy. eAML does not appear to have an independent prognostic impact; selection of post-remission therapy including allogeneic hematopoietic cell transplant (alloHCT) is typically guided by intramedullary disease risk. Management of isolated eAML should be individualized based on patient characteristics as well as eAML location and cytogenetic/molecular features. The role of PET/CT in eAML is also currently being elucidated. Improving outcomes of patients with eAML requires further knowledge of its etiology and mechanism(s) as well as therapeutic approaches beyond conventional chemotherapy, ideally in the context of controlled trials.
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Affiliation(s)
- Rory M Shallis
- Section of Hematology, Department of Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, USA
| | - Robert P Gale
- Haematology Section, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK
| | - Hillard M Lazarus
- Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Kenneth B Roberts
- Department of Radiation Oncology, Yale University School of Medicine, New Haven, USA
| | - Mina L Xu
- Department of Pathology, Yale University School of Medicine, New Haven, USA
| | - Stuart E Seropian
- Section of Hematology, Department of Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, USA
| | - Steven D Gore
- Section of Hematology, Department of Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, USA
| | - Nikolai A Podoltsev
- Section of Hematology, Department of Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, USA.
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11
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Comparison of central nervous system relapse outcomes following haploidentical vs identical-sibling transplant for acute lymphoblastic leukemia. Ann Hematol 2020; 99:1643-1653. [PMID: 32458063 DOI: 10.1007/s00277-020-04080-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Accepted: 05/04/2020] [Indexed: 12/15/2022]
Abstract
To explore the incidence, risk factors, and outcomes of central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and to compare the differences in CNS relapse between haploidentical donor HSCT (HID-HSCT) and HLA-identical sibling donor HSCT (ISD-HSCT). We performed a retrospective nested case-control study on patients with CNS relapse after allo-HSCT. The cumulative incidence of CNS relapse was 4.06% after allo-HSCT in ALL, with a significantly poor prognosis. The incidence was 3.91% and 5.36% in HID-HSCT and ISD-HSCT, respectively (p = .227). Among the patients with CNS relapse, the overall survival (OS) at 3 years was 56.2 ± 6.8% in the HID-HSCT subgroup and 76.9 ± 10.2% in the ISD-HSCT subgroup (p = .176). The 3-year cumulative incidence of systemic relapse was also comparable between the two subgroups (HID-HSCT, 40.6 ± 7.4%; ISD-HSCT, 13.3 ± 8.7%, respectively, p = .085). Younger age (p = .045), T-ALL (p = .035), hyperleukocytosis at diagnosis (p < .001), advanced disease stage at transplant (p < .001), pre-HSCT CNS involvement (p < .001), and absence of chronic graft vs host disease (cGVHD) (p < .001) were independent risk factors for CNS relapse after allo-HSCT. In conclusion, CNS relapse was a significant complication after allo-HSCT in ALL and was associated with poor prognosis. The incidences and outcomes were comparable between HID-HSCT and ISD-HSCT.
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12
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Sakellari I, Gavriilaki E, Batsis I, Mallouri D, Gavriilaki M, Apostolou C, Iskas M, Voutiadou G, Bouziana S, Bousiou Z, Constantinou V, Masmanidou M, Sotiropoulos D, Yannaki E, Lalayanni C, Pilavaki M, Chatziioannou K, Papayannopoulos S, Anagnostopoulos A. Isolated Extramedullary Relapse as a Poor Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia. Biol Blood Marrow Transplant 2019; 25:1756-1760. [DOI: 10.1016/j.bbmt.2019.05.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Revised: 04/14/2019] [Accepted: 05/19/2019] [Indexed: 12/14/2022]
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13
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Extramedullary Relapse of Acute Myelogenous Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2019; 25:1152-1157. [DOI: 10.1016/j.bbmt.2019.01.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 01/04/2019] [Indexed: 12/21/2022]
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14
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Xie N, Zhou J, Zhang Y, Yu F, Song Y. Extramedullary relapse of leukemia after allogeneic hematopoietic stem cell transplantation: A retrospective study. Medicine (Baltimore) 2019; 98:e15584. [PMID: 31083240 PMCID: PMC6531281 DOI: 10.1097/md.0000000000015584] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Extramedullary relapse (EMR) rarely occurs after allogeneic hematopoietic stem cell transplantation (HSCT) in leukemia. This study was to investigate the clinical characteristics of EMR.We retrospectively investigated 316 consecutive patients undergoing HSCT for acute leukemia or chronic myeloid leukemia (CML) at 2 institutions between January 2012 and February 2017. Furthermore, we analyzed and compared the risk factors and outcomes between EMR and bone marrow relapse (BMR).The 5-year cumulative incidence of EMR was 14.1%. The EMR incidence in acute myeloid leukemia, lymphoblastic leukemia, and CML was 17.5%, 18.9%, and 5.3%, respectively. CML had a lower EMR incidence rate. Compared to the BMR group, the EMR group had a longer median relapse-free time (10.5 months vs 5 months, P = .02), and the EMR group had a higher incidence rate of chronic graft-versus-host disease (50.0% vs 20.9%, P = .009). EMR had better estimated 3-year survival rates post-HSCT, and post-relapse, than did BMR (39.5% vs 9.5%, P < .001, and 21.9% vs 10.8%, P = .001). Multivariate analysis identified that adverse cytogenetics (hazard ratio [HR] = 9.034, P < .001) and extramedullary leukemia before HSCT (HR = 2.685, P = .027) were the independent risk factors for EMR after HSCT. In the EMR group, patients who achieved complete remission (CR) had a significantly better, estimated 3-year survival than did patients who did not achieve CR (38.4% vs 14.3%, P = .014).EMR is a significant contributor to mortality after HSCT, which appears to be resistant to most of the current therapies. Establishing effective strategies for EMR is important in improving outcomes after HSCT.
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Affiliation(s)
- Ning Xie
- Department of Hematology, The First Affiliated Hospital of Zhengzhou University
| | - Jian Zhou
- Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yanli Zhang
- Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Fengkuan Yu
- Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yongping Song
- Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
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15
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Wang Y, Chen H, Chen J, Han M, Hu J, Jiong Hu, Huang H, Lai Y, Liu D, Liu Q, Liu T, Jiang M, Ren H, Song Y, Sun Z, Wang C, Wang J, Wu D, Xu K, Zhang X, Xu L, Liu K, Huang X. The consensus on the monitoring, treatment, and prevention of leukemia relapse after allogeneic hematopoietic stem cell transplantation in China. Cancer Lett 2018; 438:63-75. [PMID: 30217562 DOI: 10.1016/j.canlet.2018.08.030] [Citation(s) in RCA: 116] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 07/29/2018] [Accepted: 08/28/2018] [Indexed: 02/05/2023]
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important curative therapy for patients with leukemia. However, relapse remains the leading cause of death after transplantation. In recent years, substantial progress has been made by Chinese physicians in the field of establishment of novel transplant modality, patient selection, minimal residual disease (MRD) monitoring, and immunological therapies, such as modified donor lymphocyte infusion (DLI) and chimeric antigen receptor T (CART) cells, as well as MRD-directed intervention for relapse. Most of these unique systems are distinct from those in the Western world. In this consensus, we reviewed the efficacy of post-HSCT relapse management practice from available Chinese studies on behalf of the HSCT workgroup of the Chinese Society of Hematology, Chinese Medical Association, and compared these studies withthe consensus or guidelines outside China. We summarized the consensus on routine practices of post-HSCT relapse management in China and focused on the recommendations of MRD monitoring, risk stratification directed strategies, and modified DLI system. This consensus will likely contribute to the standardization of post-HSCT relapse management in China and become an inspiration for further international cooperation to refine global practices.
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Affiliation(s)
- Yu Wang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital & Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, PR China
| | - Hu Chen
- Affiliated Hospital of The Academy of Military Medical Sciences, Beijing, PR China
| | - Jing Chen
- Shanghai Children's Medical Center, Shanghai, PR China
| | - Mingzhe Han
- Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Hematology and Blood Disease Hospital, Tianjin, PR China
| | - JianDa Hu
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, PR China
| | - Jiong Hu
- Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, PR China
| | - He Huang
- First Affiliated Hospital of Zhejiang University, Hangzhou, PR China
| | - Yongrong Lai
- The First Affiliated Hospital of Guangxi Medical University, Nanning, PR China
| | - Daihong Liu
- General Hospital of PLA(People's Liberation Army of China), Beijing, PR China
| | - Qifa Liu
- Nanfang Hospital of Southern Medical University, Guangzhou, PR China
| | - Ting Liu
- West China Hospital, Sichuan University, Chengdu, PR China
| | - Ming Jiang
- The First Affiliated Hospital of Xinjiang Medical University, Urumqi, PR China
| | - Hanyun Ren
- Peking University First Hospital, Beijing, PR China
| | - Yongping Song
- Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Zimin Sun
- Anhui Provincial Hospital, Hefei, PR China
| | - Chun Wang
- Shanghai Jiaotong University Affiliated No.1, People's Hospital, Shanghai, PR China
| | - Jianmin Wang
- Changhai Hospital, Second Military Medical University, Shanghai, PR China
| | - Depei Wu
- The First Affiliated Hospital of Soochow University, Soochow, PR China
| | - Kailin Xu
- The First Affiliated Hospital of Xuzhou Medical University, Xuzhou, PR China
| | - Xi Zhang
- Xinqiao Hospital, Army Medical University, Chongqing, PR China
| | - Lanping Xu
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital & Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, PR China
| | - Kaiyan Liu
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital & Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, PR China
| | - Xiaojun Huang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital & Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, PR China; Peking-Tsinghua Center for Life Sciences, Beijing, PR China.
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16
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Extramedullary relapses of acute leukemias after allogeneic hematopoietic stem cell transplantation: clinical features, cumulative incidence, and risk factors. Bone Marrow Transplant 2018; 54:595-600. [PMID: 30116013 DOI: 10.1038/s41409-018-0303-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 05/30/2018] [Accepted: 07/06/2018] [Indexed: 12/12/2022]
Abstract
The aim of this study was to evaluate extramedullary (EM) relapses and its features in an allogeneic hematopoietic stem cell transplantation (alloHSCT) cohort, which consisted of patients with acute leukemia and advanced-phase chronic myeloid leukemia. One hundred and twenty-eight alloHSCT patients transplanted between the years 2001 and 2014 were analyzed. EM relapses observed in acute lymphoblastic leukemia (ALL) were more frequent than that of in acute myeloid leukemia (AML) and CML, although calculation of cumulative risk incidence, BM relapse, EM relapse, and non-relapse mortality were considered as competing risks of each other. At the 60th month, estimated CBMR and CEMR incidences were, respectively, 14.3 (5.1)% and 25.9 (6.6)% in ALL, 25.8 (5.9)% and 15.5 (4.8)% in AML, and 61.5 (16.5)% and 17.9 (13.4)% in CML. Among multiple parameters, the only type of conditioning regimen (p:0.046), EM involvement at diagnosis (p:0.009), and the presence of GVHD were found to be associated with EM relapse risk independently (p:0.045). Chronic GVHD and TBI-based regimens significantly decreased the EM relapse risk, whereas it was higher with Mel/Flu and its variants. In conclusion, EM relapse is not uncommon after alloHSCT. GVHD and TBI-based regimens may prevent this complication.
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17
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Ikeuchi K, Doki N, Takao A, Hishima T, Yamada Y, Konishi T, Nagata A, Takezaki T, Kaito S, Kurosawa S, Sakaguchi M, Harada K, Yasuda S, Yoshioka K, Watakabe-Inamoto K, Igarashi A, Najima Y, Muto H, Kobayashi T, Kakihana K, Sakamaki H, Ohashi K. Extramedullary Gastric Relapse at the Time of Bone Marrow Relapse of Acute Lymphoblastic Leukemia after Allogeneic Bone Marrow Transplantation. Intern Med 2017; 56:3215-3217. [PMID: 28943549 PMCID: PMC5742396 DOI: 10.2169/internalmedicine.8646-16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively rare. The most commonly reported sites in acute lymphoblastic leukemia (ALL) patients after allo-HSCT are soft tissue and the central nervous system, and the gastrointestinal system is an uncommon site. We herein report a unique case with massive hematemesis resulting from gastrointestinal relapse of ALL after allo-HSCT. Upper gastrointestinal endoscopy showed bleeding from a 1.5-cm submucosal tumorous lesion with central ulceration on the anterior wall of the stomach. At the same time, computed tomography revealed extramedullary relapse at the breast and bilateral adrenal glands.
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Affiliation(s)
- Kazuhiko Ikeuchi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Noriko Doki
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Akinari Takao
- Gastroenterology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Tsunekazu Hishima
- Pathology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Yuta Yamada
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Tatsuya Konishi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Akihito Nagata
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Toshiaki Takezaki
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Satoshi Kaito
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Shuhei Kurosawa
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Masahiro Sakaguchi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Kaito Harada
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Shunichiro Yasuda
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Kosuke Yoshioka
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Kyoko Watakabe-Inamoto
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Aiko Igarashi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Yuho Najima
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Hideharu Muto
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Takeshi Kobayashi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Kazuhiko Kakihana
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Hisashi Sakamaki
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
| | - Kazuteru Ohashi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan
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18
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Kantarcioglu B, Bekoz HS, Ogret YD, Cakir A, Kivanc D, Oguz FS, Sargin D. Isolated extramedullary cutaneous relapse despite concomitant severe graft-vs.-host disease and tissue chimerism analysis in a patient with acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: A case report. Mol Clin Oncol 2017; 5:745-749. [PMID: 28105353 PMCID: PMC5228357 DOI: 10.3892/mco.2016.1052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Accepted: 09/23/2016] [Indexed: 12/27/2022] Open
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with acute lymphoblastic leukemia (ALL). The curative potential of allo-HSCT for ALL is, in part, due to the graft-vs.-leukemia (GVL) effect, in addition to the intensive conditioning chemo-radiotherapy. However, relapse remains the major cause of treatment failure following allo-HSCT for ALL. In the allo-HSCT setting, testing for genetic markers of hematopoietic chimerism has become a part of the routine diagnostic program. Routine chimerism analysis is usually performed in peripheral blood or bone marrow; in fact, little is known about the value of tissue chimerism in patients with extramedullary relapse (EMR) after the allo-HSCT setting. The present study reports on, a case of a patient with ALL who experienced isolated cutaneous EMR despite ongoing graft-vs.-host disease (GVHD), and the results of peripheral blood and skin tissue chimerism studies using multiplex polymerase chain reaction (PCR) of short tandem repeats (STR-PCR). The present case demonstrates that, although complete remission and/or chimerism may be achieved in the bone marrow, chimerism achieved at the tissue level, and the subsequent GVL effect, may be limited, despite concomitant severe GVHD following allo-HSCT. Our tissue chimerism analysis results provide a good example of how skin tissue may be a ‘sanctuary’ site for effector cells of GVL, despite active GVHD and complete hematopoetic chimerism.
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Affiliation(s)
- Bulent Kantarcioglu
- Department of Internal Medicine, Division of Hematology, Istanbul Medipol University, Istanbul 34214, Turkey
| | - Huseyin Saffet Bekoz
- Department of Internal Medicine, Division of Hematology, Istanbul Medipol University, Istanbul 34214, Turkey
| | - Yeliz Duvarci Ogret
- Istanbul Medical Faculty, Department of Medical Biology, Istanbul University, Istanbul 34214, Turkey
| | - Asli Cakir
- Department of Pathology, Istanbul Medipol University, Istanbul 34214, Turkey
| | - Demet Kivanc
- Department of Internal Medicine, Division of Hematology, Istanbul Medipol University, Istanbul 34214, Turkey
| | - Fatma Savran Oguz
- Istanbul Medical Faculty, Department of Medical Biology, Istanbul University, Istanbul 34214, Turkey
| | - Deniz Sargin
- Department of Internal Medicine, Division of Hematology, Istanbul Medipol University, Istanbul 34214, Turkey
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19
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[The consensus of allogeneic hematopoietic transplantation for hematological diseases in China(2016)-- post- transplant leukemia relapse]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2016; 37:846-851. [PMID: 27801312 PMCID: PMC7364870 DOI: 10.3760/cma.j.issn.0253-2727.2016.10.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/03/2016] [Indexed: 11/29/2022]
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20
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Demirsoy ET, Atesoglu EB, Tarkun P, Gedük A, Erdem BE, Hacihanefioglu A, Erçin MC. Isolated Breast Relapse of Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation. Indian J Hematol Blood Transfus 2016; 32:201-4. [PMID: 27408391 PMCID: PMC4925511 DOI: 10.1007/s12288-015-0560-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2015] [Accepted: 05/26/2015] [Indexed: 12/27/2022] Open
Abstract
Isolated breast relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is less often seen. Chronic graft-versus-host disease (cGVHD) is effective in preventing marrow relapse, but cGVHD seems not to be effective extramedullary relapse (EMR). We report the case of isolated breast relapse after first allo-HSCT for acute lymphoblastic leukemia (ALL). A 47-year-old female was diagnosed with ALL achieved complete remission with salvage chemotherapy and underwent allo-HSCT from an HLA-matched sibling male donor. At 17 months post-transplant, she presented with a bilateral breast masses that confirmed the diagnosis lymphoblast involvement. She had no evidence of leukemia in her marrow that determined 100 % full-donor chimerism when she was relapsed in her both breasts.
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Affiliation(s)
- Esra Terzi Demirsoy
- />Department of Hematology, Kocaeli University School of Medicine, Umuttepe, Kocaeli 41380 Turkey
| | - Elif Birtas Atesoglu
- />Department of Hematology, Kocaeli University School of Medicine, Umuttepe, Kocaeli 41380 Turkey
| | - Pinar Tarkun
- />Department of Hematology, Kocaeli University School of Medicine, Umuttepe, Kocaeli 41380 Turkey
| | - Ayfer Gedük
- />Department of Hematology, Kocaeli University School of Medicine, Umuttepe, Kocaeli 41380 Turkey
| | - Büşra Erşan Erdem
- />Department of Patology, Kocaeli University School of Medicine, Umuttepe, Kocaeli 41380 Turkey
| | - Abdullah Hacihanefioglu
- />Department of Hematology, Kocaeli University School of Medicine, Umuttepe, Kocaeli 41380 Turkey
| | - Mehmet Cengiz Erçin
- />Department of Patology, Kocaeli University School of Medicine, Umuttepe, Kocaeli 41380 Turkey
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21
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Yanagisawa R, Nakazawa Y, Sakashita K, Saito S, Tanaka M, Shiohara M, Shimodaira S, Koike K. Intrathecal donor lymphocyte infusion for isolated leukemia relapse in the central nervous system following allogeneic stem cell transplantation: a case report and literature review. Int J Hematol 2015; 103:107-11. [DOI: 10.1007/s12185-015-1902-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 11/04/2015] [Accepted: 11/09/2015] [Indexed: 10/22/2022]
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22
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Extramedullary Relapse of Acute Leukemia after Haploidentical Hematopoietic Stem Cell Transplantation: Incidence, Risk Factors, Treatment, and Clinical Outcomes. Biol Blood Marrow Transplant 2014; 20:2023-8. [DOI: 10.1016/j.bbmt.2014.08.023] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2014] [Accepted: 08/30/2014] [Indexed: 11/22/2022]
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23
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Ge L, Ye F, Mao X, Chen J, Sun A, Zhu X, Qiu H, Jin Z, Miao M, Fu C, Ma X, Chen F, Xue S, Ruan C, Wu D, Tang X. Extramedullary relapse of acute leukemia after allogeneic hematopoietic stem cell transplantation: different characteristics between acute myelogenous leukemia and acute lymphoblastic leukemia. Biol Blood Marrow Transplant 2014; 20:1040-7. [PMID: 24704575 DOI: 10.1016/j.bbmt.2014.03.030] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Accepted: 03/25/2014] [Indexed: 12/19/2022]
Abstract
Extramedullary relapse (EMR) of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a contributor to post-transplantation mortality and remains poorly understood, especially the different characteristics of EMR in patients with acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia (ALL). To investigate the incidence, risk factors, and clinical outcomes of EMR for AML and ALL, we performed a retrospective analysis of 362 patients with AL who underwent allo-HSCT at the First affiliated Hospital of Soochow University between January 2001 and March 2012. Compared with patients with AML, those with ALL had a higher incidence of EMR (12.9% versus 4.6%; P = .009). The most common site of EMR was the central nervous system, especially in the ALL group. Multivariate analyses identified the leading risk factors for EMR in the patients with AML as advanced disease status at HSCT, hyperleukocytosis at diagnosis, history of extramedullary leukemia before HSCT, and a total body irradiation-based conditioning regimen, and the top risk factors for EMR in the patients with ALL as hyperleukocytosis at diagnosis, adverse cytogenetics, and transfusion of peripheral blood stem cells. The prognosis for EMR of AL is poor, and treatment options are very limited; however, the estimated 3-year overall survival (OS) was significantly lower in patients with AML compared with those with ALL (0 versus 18.5%; P = .000). The characteristics of post-allo-HSCT EMR differed between the patients with AML and those with ALL, possibly suggesting different pathogenetic mechanisms for EMR of AML and EMR of ALL after allo-HSCT; further investigation is needed.
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Affiliation(s)
- Ling Ge
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Fan Ye
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Xinliang Mao
- Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
| | - Jia Chen
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Aining Sun
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Xiaming Zhu
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Huiying Qiu
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Zhengming Jin
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Miao Miao
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Chengcheng Fu
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Xiao Ma
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Feng Chen
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Shengli Xue
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Changgeng Ruan
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China
| | - Depei Wu
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
| | - Xiaowen Tang
- Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
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