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Impact of HLA-mismatched unrelated transplantation in patients with adult T-cell leukemia/lymphoma


This Japanese nationwide retrospective study investigated the impact of HLA-mismatched unrelated transplantation for adult T-cell leukemia-lymphoma (ATL) patients who received transplantation between 2000 and 2018. We compared 6/6 antigen-matched related donor (MRD), 8/8 allele-matched unrelated donor (8/8MUD), and 1 allele-mismatched unrelated donor (7/8MMUD) in the graft-versus-host direction. We included 1191 patients; 449 (37.7%) were in the MRD group, 466 (39.1%) in the 8/8MUD group, and 276 (23.7%) in the 7/8MMUD group. In the 7/8MMUD group, 97.5% of patients received bone marrow transplantation, and no patients received post-transplant cyclophosphamide. The cumulative incidences of non-relapse mortality (NRM) and relapse at 4 years, and the probabilities of overall survival at 4 years in the MRD group were 24.7%, 44.4%, 37.5%, in the 8/8MUD group were 27.2%, 38.2%, and 37.9%, and in the 7/8MMUD group were 34.0%, 34.4%, and 35.3%, respectively. The 7/8MMUD group had a higher risk of NRM (hazard ratio (HR) 1.50 [95% CI, 1.13–1.98; P = 0.005]) and a lower risk of relapse (HR 0.68 [95% CI, 0.53–0.87; P = 0.003]) than the MRD group. The donor type was not a significant risk factor for overall mortality. These data suggest that 7/8MMUD is an acceptable alternative donor when an HLA-matched donor is unavailable.

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Fig. 1: Cumulative incidences of GVHD.
Fig. 2: Cumulative incidences of NRM and relapse, and the probability of OS and GRFS.
Fig. 3: Impact of donor type on outcomes by each factor, comparing the 8/8MUD and 7/8MMUD groups.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


  1. Anasetti C, Beatty PG, Storb R, Martin PJ, Mori M, Sanders JE, et al. Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. Hum Immunol. 1990;29:79–91.

    Article  CAS  PubMed  Google Scholar 

  2. Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997;15:1767–77.

    Article  CAS  PubMed  Google Scholar 

  3. Kanda Y, Chiba S, Hirai H, Sakamaki H, Iseki T, Kodera Y, et al. Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000). Blood. 2003;102:1541–7.

    Article  CAS  PubMed  Google Scholar 

  4. Kanda J, Saji H, Fukuda T, Kobayashi T, Miyamura K, Eto T, et al. Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation: a nationwide retrospective study. Blood. 2012;119:2409–16.

    Article  CAS  PubMed  Google Scholar 

  5. Kanda Y, Kanda J, Atsuta Y, Maeda Y, Ichinohe T, Ohashi K, et al. Impact of a single human leucocyte antigen (HLA) allele mismatch on the outcome of unrelated bone marrow transplantation over two time periods. A retrospective analysis of 3003 patients from the HLA Working Group of the Japan Society for Blood and Marrow Transplantation. Br J Haematol. 2013;161:566–77.

    Article  CAS  PubMed  Google Scholar 

  6. Kekre N, Antin JH. Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist. Blood. 2014;124:334–43.

    Article  CAS  PubMed  Google Scholar 

  7. Bachanova V, Burns LJ, Wang T, Carreras J, Gale RP, Wiernik PH, et al. Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor. Bone Marrow Transpl. 2015;50:197–203.

    Article  CAS  Google Scholar 

  8. Cook LB, Fuji S, Hermine O, Bazarbachi A, Ramos JC, Ratner L, et al. Revised adult T-cell leukemia-lymphoma international consensus meeting report. J Clin Oncol. 2019;37:677–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fuji S, Kurosawa S, Inamoto Y, Murata T, Utsunomiya A, Uchimaru K, et al. Role of up-front allogeneic hematopoietic stem cell transplantation for patients with aggressive adult T-cell leukemia-lymphoma: a decision analysis. Bone Marrow Transpl. 2018;53:905–8.

    Article  CAS  Google Scholar 

  10. Utsunomiya A. Progress in allogeneic hematopoietic cell transplantation in adult T-cell leukemia-lymphoma. Front Microbiol. 2019;10:2235

    Article  PubMed  PubMed Central  Google Scholar 

  11. Iqbal M, Reljic T, Klocksieben F, Sher T, Ayala E, Murthy H, et al. Corrigendum to ‘Efficacy of allogeneic HCT in HTLV-1 associated adult T-cell leukemia/lymphoma: results of a systematic review/meta-analysis’. Biol Blood Marrow Transplant. 2020;26:209–12.

  12. Kanda J, Hishizawa M, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y, et al. Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study. Blood. 2012;119:2141–8.

    Article  CAS  PubMed  Google Scholar 

  13. Tanosaki R, Uike N, Utsunomiya A, Saburi Y, Masuda M, Tomonaga M, et al. Allogeneic hematopoietic stem cell transplantation using reduced-intensity conditioning for adult T cell leukemia/lymphoma: impact of antithymocyte globulin on clinical outcome. Biol Blood Marrow Transpl. 2008;14:702–8.

    Article  CAS  Google Scholar 

  14. Yoshimitsu M, Utsunomiya A, Fuji S, Fujiwara H, Fukuda T, Ogawa H, et al. A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia-lymphoma. Bone Marrow Transplant 2018.

  15. Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, et al. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System. Int J Hematol. 2007;86:269–74.

    Article  PubMed  Google Scholar 

  16. Atsuta Y. Atsuta Y. Introduction of transplant registry unified management program 2 (TRUMP2): scripts for TRUMP data analyses, part I (variables other than HLA-related data. Int J Hematol. 2016;103:3–10.

  17. Kanda J. Scripts for TRUMP data analyses. Part II (HLA-related data): statistical analyses specific for hematopoietic stem cell transplantation. Int J Hematol. 2016;103:11–19.

    Article  CAS  PubMed  Google Scholar 

  18. Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol. 1991;79:428–37.

    Article  CAS  PubMed  Google Scholar 

  19. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transpl. 2009;15:1628–33.

    Article  Google Scholar 

  20. Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transpl. 2009;15:367–9.

    Article  Google Scholar 

  21. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transpl. 1995;15:825–8.

    CAS  Google Scholar 

  23. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.

    Article  CAS  PubMed  Google Scholar 

  24. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transpl. 2005;11:945–56.

    Article  Google Scholar 

  25. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health Consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transpl. 2015;21:389–401.e381.

    Article  Google Scholar 

  26. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.

    Article  CAS  Google Scholar 

  27. Fuji S, Yamaguchi T, Inoue Y, Utsunomiya A, Moriuchi Y, Uchimaru K, et al. Development of a modified prognostic index for patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: possible risk-adapted management strategies including allogeneic transplantation. Haematologica. 2017;102:1258–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fuji S, Fujiwara H, Nakano N, Wake A, Inoue Y, Fukuda T, et al. Early application of related SCT might improve clinical outcome in adult T-cell leukemia/lymphoma. Bone Marrow Transpl. 2016;51:205–11.

    Article  CAS  Google Scholar 

  29. Inoue Y, Fuji S, Tanosaki R, Inamoto Y, Tanaka T, Ito A, et al. Prognostic importance of pretransplant disease status for posttransplant outcomes in patients with adult T cell leukemia/lymphoma. Bone Marrow Transpl. 2018;53:1105–15.

    Article  CAS  Google Scholar 

  30. Pidala J, Lee SJ, Ahn KW, Spellman S, Wang HL, Aljurf M, et al. Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation. Blood. 2014;124:2596–606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Verneris MR, Lee SJ, Ahn KW, Wang HL, Battiwalla M, Inamoto Y, et al. HLA mismatch is associated with worse outcomes after unrelated donor reduced-intensity conditioning hematopoietic cell transplantation: an analysis from the center for international blood and marrow transplant research. Biol Blood Marrow Transpl. 2015;21:1783–9.

    Article  Google Scholar 

  32. Katsuya H, Yamanaka T, Ishitsuka K, Utsunomiya A, Sasaki H, Hanada S, et al. Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma. J Clin Oncol. 2012;30:1635–40.

    Article  CAS  PubMed  Google Scholar 

  33. Young JH, Logan BR, Wu J, Wingard JR, Weisdorf DJ, Mudrick C, et al. Infections after transplantation of bone marrow or peripheral blood stem cells from unrelated donors. Biol Blood Marrow Transpl. 2016;22:359–70.

    Article  Google Scholar 

  34. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N. Engl J Med. 2012;367:1487–96.

    Article  CAS  PubMed  Google Scholar 

  35. Nagafuji K, Matsuo K, Teshima T, Mori S, Sakamaki H, Hidaka M, et al. Peripheral blood stem cell versus bone marrow transplantation from HLA-identical sibling donors in patients with leukemia: a propensity score-based comparison from the Japan Society for Hematopoietic Stem Cell Transplantation registry. Int J Hematol. 2010;91:855–64.

    Article  PubMed  Google Scholar 

  36. Stem Cell Trialists’ Collaborative G. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol. 2005;23:5074–87.

    Article  Google Scholar 

  37. Inoue Y, Okinaka K, Fuji S, Inamoto Y, Uchida N, Toya T, et al. Severe acute graft-versus-host disease increases the incidence of blood stream infection and mortality after allogeneic hematopoietic cell transplantation: Japanese transplant registry study. Bone Marrow Transpl. 2021;56:2125–36.

    Article  Google Scholar 

  38. Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, et al. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol Blood Marrow Transpl. 2012;18:1859–66.

    Article  Google Scholar 

  39. Sugita J, Kawashima N, Fujisaki T, Kakihana K, Ota S, Matsuo K, et al. HLA-haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide after Busulfan-containing reduced-intensity conditioning. Biol Blood Marrow Transpl. 2015;21:1646–52.

    Article  Google Scholar 

  40. Sugita J, Kagaya Y, Miyamoto T, Shibasaki Y, Nagafuji K, Ota S, et al. Myeloablative and reduced-intensity conditioning in HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide. Bone Marrow Transpl. 2019;54:432–41.

    Article  CAS  Google Scholar 

  41. Al Malki MM, Tsai NC, Palmer J, Mokhtari S, Tsai W, Cao T, et al. Posttransplant cyclophosphamide as GVHD prophylaxis for peripheral blood stem cell HLA-mismatched unrelated donor transplant. Blood Adv. 2021;5:2650–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Battipaglia G, Labopin M, Kröger N, Vitek A, Afanasyev B, Hilgendorf I, et al. Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation. Blood. 2019;134:892–9.

    Article  CAS  PubMed  Google Scholar 

  43. Nykolyszyn C, Granata A, Pagliardini T, Castagna L, Harbi S, Bouabdallah R, et al. Posttransplantation cyclophosphamide vs. antithymocyte globulin as GVHD prophylaxis for mismatched unrelated hematopoietic stem cell transplantation. Bone Marrow Transpl. 2020;55:349–55.

    Article  CAS  Google Scholar 

  44. Gao F, Zhang J, Hu J, Lin L, Xu Y. Post-transplant cyclophosphamide versus antithymocyte globulin in allogeneic hematopoietic cell transplantation: a meta-analysis. Ann Hematol. 2021;100:529–40.

    Article  CAS  PubMed  Google Scholar 

  45. Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N. Engl J Med. 1986;314:729–35.

    Article  CAS  PubMed  Google Scholar 

  46. Tanaka Y, Kurosawa S, Tajima K, Tanaka T, Ito R, Inoue Y, et al. Analysis of non-relapse mortality and causes of death over 15 years following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transpl. 2016;51:553–9.

    Article  CAS  Google Scholar 

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This research was supported by JSPS KAKENHI Grant Number 19K17861 and 22K16305, and by the Practical Research for Innovative Cancer Control Program of the Japan Agency for Medical Research and Development (20ck0106616h0001). We are grateful to the ATL Working Group of the JSTCT and the data management committee of TRUMP by the JSTCT and the JDCHCT for helping with this study.

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YI, SM, KK, TF, and MY participated in the research design, data analysis, and writing of this article. AI, NN, TK, TK, YM, YS, HI, YM, KI, ST, JK, TI, and YA participated in writing of the paper.

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Correspondence to Yoshitaka Inoue.

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JK has received honoraria (e.g., lecture fees) from Sanofi. The other authors declare no competing interests.

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Inoue, Y., Morishima, S., Kato, K. et al. Impact of HLA-mismatched unrelated transplantation in patients with adult T-cell leukemia/lymphoma. Bone Marrow Transplant 58, 980–990 (2023).

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