Abstract

Currently, allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only available curative modality for patients with adult T-cell leukemia–lymphoma (ATL). When used in conjunction with posttransplantation cyclophosphamide (PTCY) for graft-versus-host disease prophylaxis, allo-HCT from an HLA haplo-identical donor yields promising outcomes for many diseases other than ATL. However, appropriate comparisons with other donor sources, especially cord blood and conventional HLA haplo-identical donors, are needed to validate the safety and efficacy of this modality. In this study, we retrospectively evaluated the outcome of allo-HCT without PTCY in patients with ATL registered in the Japan Society for Hematopoietic Cell Transplantation TRUMP database between 1985 and 2015. During that period, 46 patients received allo-HCT without PTCY and survivors were followed for a median of 2316.5 days (range: 220–3884 days). Although the estimated 1- and 5-year overall survival rates of the entire cohort were 34.5% and 17.7%, respectively, the cumulative 1- and 5-year non-ATL mortality rates of 41.3% and 55.8%, respectively, were high. The results of our study will serve as a platform for discussions of the safety and efficacy of haplo-HCT for future clinical trials in patients with ATL.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Utsunomiya A, Miyazaki Y, Takatsuka Y, Hanada S, Uozumi K, Yashiki S, et al. Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;27:15–20. https://doi.org/10.1038/sj.bmt.1702731.

  2. 2.

    Ishitsuka K, Tamura K. Human T-cell leukaemia virus type I and adult T-cell leukaemia-lymphoma. Lancet Oncol. 2014;15:e517–526. https://doi.org/10.1016/s1470-2045(14)70202-5.

  3. 3.

    Bazarbachi A, Cwynarski K, Boumendil A, Finel H, Fields P, Raj K, et al. Outcome of patients with HTLV-1-associated adult T-cell leukemia/lymphoma after SCT: a retrospective study by the EBMT LWP. Bone Marrow Transplant. 2014;49:1266–8. https://doi.org/10.1038/bmt.2014.143.

  4. 4.

    Phillips EH, Hodson A, Hermine O, Bazarbachi A, Cwynarski K. Striving to cure adult T-cell leukaemia/lymphoma: a role for allogeneic stem cell transplant? Bone Marrow Transplant. 2016;51:1549–55. https://doi.org/10.1038/bmt.2016.154.

  5. 5.

    Hishizawa M, Kanda J, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y, et al. Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study. Blood. 2010;116:1369–76. https://doi.org/10.1182/blood-2009-10-247510.

  6. 6.

    Fuji S, Inoue Y, Utsunomiya A, Moriuchi Y, Uchimaru K, Choi I, et al. Pretransplantation anti-CCR4 antibody mogamulizumab against adult T-cell leukemia/lymphoma is associated with significantly increased risks of severe and corticosteroid-refractory graft-versus-host disease, nonrelapse mortality, and overall mortality. J Clin Oncol. 2016;34:3426–33. https://doi.org/10.1200/jco.2016.67.8250.

  7. 7.

    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 Transplant. 2018;53:1105–15. https://doi.org/10.1200/jco.2016.67.8250.

  8. 8.

    Yoshimitsu M, Tanosaki R, Kato K, Ishida T, Choi I, Takatsuka Y et al. Risk Assessment in Adult T Cell Leukemia/Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2018; 24(4): 832-839. e-pub ahead of print 2017/11/21; https://doi.org/10.1016/j.bbmt.2017.11.005.

  9. 9.

    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 Transplant. 2016;51:205–11. https://doi.org/10.1038/bmt.2015.265.

  10. 10.

    Kato K, Choi I, Wake A, Uike N, Taniguchi S, Moriuchi Y et al. Treatment of patients with adult T cell leukemia/lymphoma with cord blood transplantation: a Japanese nationwide retrospective survey. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2014; 20(12): 1968-1974. e-pub ahead of print 2014/08/31; https://doi.org/10.1016/j.bbmt.2014.08.012.

  11. 11.

    Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–50. https://doi.org/10.1016/j.bbmt.2008.03.005.

  12. 12.

    O’Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8:377–86.

  13. 13.

    Kasamon YL, Bolanos-Meade J, Prince GT, Tsai HL, McCurdy SR, Kanakry JA, et al. Outcomes of nonmyeloablative HLA-haploidentical blood or marrow transplantation with high-dose post-transplantation cyclophosphamide in older adults. J Clin Oncol. 2015;33:3152–61. https://doi.org/10.1200/jco.2014.60.4777.

  14. 14.

    Ghosh N, Ye X, Tsai HL, Bolanos-Meade J, Fuchs EJ, Luznik L, et al. Allogeneic blood or marrow transplantation with post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis in multiple myeloma. Biol Blood Marrow Transplant. 2017;23:1903–9. https://doi.org/10.1016/j.bbmt.2017.07.003

  15. 15.

    Obama K, Utsunomiya A, Takatsuka Y, Takemoto Y. Reduced-intensity non-T-cell depleted HLA-haploidentical stem cell transplantation for older patients based on the concept of feto-maternal tolerance. Bone Marrow Transplant. 2004;34:897–9. https://doi.org/10.1038/sj.bmt.1704692.

  16. 16.

    Fujiwara H, Ozaki A, Yoshimitsu M, Hamada H, Masamoto I, Matsushita K, et al. Allogeneic stem cell transplantation for refractory adult T-cell leukemia using a non-T-cell-depleted HLA-incompatible family donor graft, with reference to the grown-up child donor to parent recipient setting: report of a pilot study. Int J Hematol. 2008;87:319–26. https://doi.org/10.1007/s12185-008-0042-2.

  17. 17.

    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 Transplant. 2009;15:367–9. https://doi.org/10.1016/j.bbmt.2008.12.497.

  18. 18.

    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 Transplant. 2009;15:1628–33. https://doi.org/10.1016/j.bbmt.2009.07.004.

  19. 19.

    Iacobelli S. Suggestions on the use of statistical methodologies in studies of the European Group for Blood and Marrow Transplantation. Bone marrow transplantation 2013; 48 Suppl 1: S1-37. e-pub ahead of print 2013/03/15; https://doi.org/10.1038/bmt.2012.282.

  20. 20.

    Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone marrow transplantation 2013; 48(3): 452-458. e-pub ahead of print 2012/12/05; https://doi.org/10.1038/bmt.2012.244.

  21. 21.

    Ishida T, Hishizawa M, Kato K, Tanosaki R, Fukuda T, Taniguchi S, et al. Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study. Blood. 2012;120:1734–41. https://doi.org/10.1182/blood-2012-03-414490.

  22. 22.

    Ikegame K, Yoshida T, Yoshihara S, Daimon T, Shimizu H, Maeda Y, et al. Unmanipulated haploidentical reduced-intensity stem cell transplantation using fludarabine, busulfan, low-dose antithymocyte globulin, and steroids for patients in non-complete remission or at high risk of relapse: a prospective multicenter phase I/II study in Japan. Biol Blood Marrow Transplant. 2015;21:1495–505. https://doi.org/10.1016/j.bbmt.2015.04.012.

  23. 23.

    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 Transplant. 2018. https://doi.org/10.1038/s41409-017-0082-4.

  24. 24.

    Nosaka K, Iwanaga M, Imaizumi Y, Ishitsuka K, Ishizawa K, Ishida Y et al. Epidemiological and clinical features of adult T-cell leukemia-lymphoma in Japan, 2010-1: a nationwide survey. Cancer Sci. 2017;108:2478-86. https://doi.org/10.1111/cas.13398

  25. 25.

    Arai Y, Jo T, Matsui H, Kondo T, Takaori-Kondo A. Efficacy of antithymocyte globulin for allogeneic hematopoietic cell transplantation: a systematic review and meta-analysis. Leuk Lymph. 2017;58:1840–8. https://doi.org/10.1080/10428194.2016.1266624.

  26. 26.

    Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, et al. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016;17:164–73. https://doi.org/10.1016/s1470-2045(15)00462-3.

  27. 27.

    Okamura J, Utsunomiya A, Tanosaki R, Uike N, Sonoda S, Kannagi M et al. Allogeneic stem-cell transplantation with reduced conditioning intensity as a novel immunotherapy and antiviral therapy for adult T-cell leukemia/lymphoma. Blood 2005; 105(10): 4143-4145. e-pub ahead of print 2005/01/25; https://doi.org/10.1182/blood-2004-11-4193.

  28. 28.

    Burroughs LM, O’Donnell PV, Sandmaier BM, Storer BE, Luznik L, Symons HJ, et al. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008;14:1279–87. https://doi.org/10.1016/j.bbmt.2008.08.014.

  29. 29.

    Bashey A, Zhang MJ, McCurdy SR, St Martin A, Argall T, Anasetti C, et al. Mobilized peripheral blood stem cells versus unstimulated bone marrow as a graft source for T-cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide. J Clin Oncol. 2017;35:3002–9. https://doi.org/10.1200/jco.2017.72.8428.

  30. 30.

    Srour SA, Milton DR, Bashey A, Karduss-Urueta A, Al Malki MM, Romee R, et al. Haploidentical transplantation with post-transplantation cyclophosphamide for high-risk acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2017;23:318–24. https://doi.org/10.1016/j.bbmt.2016.11.008.

Download references

Acknowledgements

We thank all the physicians and data managers at the participating institutions, who contributed valuable data on transplantation for ATL to the JSHCT. We also thank all members of the data management committees of the JSHCT.

ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation

Koji Kato, Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan. Takashi Ishida, Division of Hematology and Oncology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan. Atae Utsunomiya, Department of Hematology, Imamura General Hospital, Kagoshima, Japan. Junji Suzumiya, Innovative Cancer Center/Oncology-Hematology, Shimane University Hospital, Izumo, Japan. Yoshifusa Takatsuka, Department of Hematology, Izuro Imamura Hospital, Kagoshima, Japan. Tomomi Tobai, Department of Internal Medicine III, Division of Hematology and Cell Therapy, Yamagata University Faculty of Medicine, Yamagata, Japan. Koichi Nakase, Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan. Yuichiro Nawa, Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan. Masakatsu Hishizawa, Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Takuya Fukushima, Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan. Laboratory of Hematoimmunology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Nishihara, Japan. Masato Masuda, Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan. Cancer Centre, University of the Ryukyus, Nishihara, Japan. Atsushi Wake, Department of Hematology, Toranomon Hospital Kajigaya, Kawasaki, Japan. Choi Ilseung, Department of Hematology, National Kyushu Cancer Center, Fukuoka, Japan. Yoshitaka Asakura, Department of Hematology, Okinawa Red Cross Hospital, Naha, Japan. Nobuaki Nakano, Department of Hematology, Imamura General Hospital, Kagoshima, Japan. Hiroshi Fujiwara, Department of Immuno-gene therapy, Center for Comprehensive Cancer Immunotherapy, Mie University Graduate School of Medicine, Tsu, Japan. Shinichiro Machida, Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan. Yasushi Sawayama, Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan. Kohei Tada, Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. Yoshitaka Inoue, Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan. Kazunori Imada, Department of Hematology, Osaka Red Cross Hospital, Osaka, Japan. Isao Yoshida, Department of Hematologic Oncology, Shikoku Cancer Center, Matsuyama, Japan. Makoto Yoshimitsu, Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan. Shigeo Fuji, Department of Hematology, Osaka International Cancer Center, Osaka, Japan. Takahiro Fukuda, Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. Takero Shindo, Department of Hematology/Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Masahito Tokunaga, Department of Hematology, Imamura General Hospital, Kagoshima, Japan. Hiroyuki Muranushi, Department of Hematology/Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Satoko Morishima, Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan. Shohei Tomori, Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan. Tomoki Iemura, Department of Hematology/Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Author contributions

MY, AU, SF, HF, TF, and KK designed the research, organized the project, and wrote the paper. MY performed the statistical analyses. H Ogawa, YT, KI, AY, H Okumura, KI, AN, TE, AY, KM, J Tsukada, J Tanaka, and YA gathered the data. All authors contributed to the final version of the manuscript and have approved it for submission for publication.

Author information

Affiliations

  1. Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan

    • Makoto Yoshimitsu
    •  & Kenji Ishitsuka
  2. Department of Hematology, Imamura General Hospital, Kagoshima, Japan

    • Atae Utsunomiya
    •  & Yoshifusa Takatsuka
  3. Department of Hematology, Osaka International Cancer Center, Osaka, Japan

    • Shigeo Fuji
  4. Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University, Ehime, Japan

    • Hiroshi Fujiwara
  5. Department of Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    • Takahiro Fukuda
  6. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

    • Hiroyasu Ogawa
  7. Department of Hematology, Chiba Aoba Municipal Hospital, Chiba, Japan

    • Akira Yokota
  8. Department of Internal Medicine (Hematology), Toyama Prefectural Central Hospital, Toyama, Japan

    • Hirokazu Okumura
  9. Department of Hematology and Oncology, Kansai Medical University Medical Center, Osaka, Japan

    • Kazuyoshi Ishii
  10. Department of Hematology, Wakayama Medical University, Wakayama, Japan

    • Akinori Nishikawa
  11. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    • Tetsuya Eto
  12. Department of Hematology, Kokura Memorial Hospital, Fukuoka, Japan

    • Akihito Yonezawa
  13. Department of Hematology, National Kyushu Cancer Center, Fukuoka, Japan

    • Kaname Miyashita
  14. Department of Hematology, University of Occupational and Environmental Health, Fukuoka, Japan

    • Junichi Tsukada
  15. Department of Hematology, Tokyo Women’s Medical University, Tokyo, Japan

    • Junji Tanaka
  16. Japanese Data Center for Hematopoietic Cell Transplantation, Aichi, Japan

    • Yoshiko Atsuta
  17. Nagoya University Graduate School of Medicine, Aichi, Japan

    • Yoshiko Atsuta
  18. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan

    • Koji Kato

Authors

  1. Search for Makoto Yoshimitsu in:

  2. Search for Atae Utsunomiya in:

  3. Search for Shigeo Fuji in:

  4. Search for Hiroshi Fujiwara in:

  5. Search for Takahiro Fukuda in:

  6. Search for Hiroyasu Ogawa in:

  7. Search for Yoshifusa Takatsuka in:

  8. Search for Kenji Ishitsuka in:

  9. Search for Akira Yokota in:

  10. Search for Hirokazu Okumura in:

  11. Search for Kazuyoshi Ishii in:

  12. Search for Akinori Nishikawa in:

  13. Search for Tetsuya Eto in:

  14. Search for Akihito Yonezawa in:

  15. Search for Kaname Miyashita in:

  16. Search for Junichi Tsukada in:

  17. Search for Junji Tanaka in:

  18. Search for Yoshiko Atsuta in:

  19. Search for Koji Kato in:

Consortia

  1. on behalf of ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Corresponding author

    Correspondence to Makoto Yoshimitsu.

    About this article

    Publication history

    Received

    Revised

    Accepted

    Published

    DOI

    https://doi.org/10.1038/s41409-018-0400-5