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Dismal outcome of allogeneic hematopoietic stem cell transplantation for relapsed adult T-cell leukemia/lymphoma, a Japanese nation-wide study

Bone Marrow Transplantation volume 52, pages 484–488 (2017)Cite this article

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Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-lymphocyte malignancy caused by human T-lymphotropic virus type I (HTLV-1) infection.1 In Japan, an intensive chemotherapy such as VCAP–AMP–VECP regimen is widely applied to patients with aggressive ATL; however, the median PFS was at most 7 months.2 On the other hand, allogeneic hematopoietic stem cell transplantation (allo-HSCT) for those patients achieved several years of disease-free survival.3, 4, 5 Thus, allo-HSCT has now become an important treatment option for aggressive ATL, however, in daily practice, difficulties associated with advanced age largely limit the number of ATL patients eligible for allo-HSCT. Furthermore, the time-consuming process of acquiring a suitable unrelated donor exceeds the brief window of opportunity (controlled disease status) for allo-HSCT, because ATL tumor cells are characteristically apt to turn resistant to chemotherapeutic agents.6 Taking above, we assume that in daily practice, a substantial number of ATL patients might miss a good opportunity for allo-HSCT, instead, they might have to undergo allo-HSCT on relapsed disease. Unfortunately, previous studies uniformly divided disease status at transplant into CR vs non-CR. Therefore, in this study, we attempted to clarify outcomes of allo-HSCT for patients with relapsed ATL using information from the database of Japan Society for Hematopoietic Cell Transplantation (JSHCT). Mogamulizumab,7 a humanized anti-CCR4 monoclonal antibody which greatly impacted on the disease control of aggressive ATL, was widely introduced into daily practice in Japan in the late of 2012. Therefore, to this end, data for all patients who received a first allo-HSCT from 1985 to 2012 were obtained from the Transplant Registry Unified Management Program (TRUMP).8 This study was planned by the ATL working group of JSHCT, and was approved by the data management committees of TRUMP and the institutional review board of Ehime University and the National Cancer Center, Tokyo, Japan. A total of 131 patients with relapsed ATL met the criteria. We did not include any patients with ATL in remission. Primary end point was the probability of overall survival (OS). Secondary end points included the cumulative incidence of non-relapse mortality (NRM) and relapse. The patients’ characteristics were compared using the χ2 test or Fisher’s exact test for categorical variables. The probability of OS was analyzed by the Kaplan–Meier method, and a Cox proportional-hazards regression model. The cumulative incidence of NRM and acute GvHD were evaluated using the model of Fine and Grey the competing-risk model9 for univariate and multivariate analyses. A two-sided P-value <0.05 was considered statistically significant. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University; http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html), a graphical user interface for R (version 3.0.2; The R Foundation for Statistical Computing, Vienna, Austria).10 EZR is a modified version of R commander (version 2.0.3) that incorporates statistical functions frequently used in biostatistics.

On the other hand, in the setting of allo-HSCT for ATL, Japanese physicians tended to prefer HLA matched stem cell sources (61.8%), furthermore, 69% of those (42%) were unrelated bone marrow (Table 1). Given, the inherently longer period needed for acquisition of a suitable unrelated donor might unintentionally result in those patients missing the good opportunity with better PS (0–1) and controlled disease status, because ATL tumor cells are usually sensitive to initial chemotherapy for a while, despite being predisposed to acquire chemo-resistance.6, 11

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Acknowledgements

We thank the medical, nursing, data-processing, laboratory, and clinical staff at the participating centers. HF, SF designed research, analyzed data and wrote the paper; AW, KK and TF participated in research design; YT, JT, NU, TM, MH, YM, TT, TN, YM, TI and YA gathered the data; AU participated in research design and writing of the paper. All authors approved the submission of this study. This research is partially supported by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and development, AMED (15Ack0106136h0002).

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Author notes

  1. H Fujiwara and S Fuji: These authors contributed equally to this work.

Authors and Affiliations

  1. First Department of Internal Medicine, Ehime University Hospital, Ehime, Japan

    H Fujiwara

  2. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    S Fuji & T Fukuda

  3. Department of Hematology, Toranomon Hospital Kajigaya, Kanagawa, Japan

    A Wake

  4. Department of Hematology and Oncology, Kyushu University Hospital, Fukuoka, Japan

    K Kato & T Miyamoto

  5. Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan

    Y Takatsuka & A Utsunomiya

  6. Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Nagasaki University Hospital, Nagasaki, Japan

    J Taguchi

  7. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    N Uchida

  8. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan

    M Hidaka

  9. Department of Hematology, Oita Prefecture Hospital, Oita, Japan

    Y Miyazaki

  10. Second Department of Internal Medicine, University Hospital, University of the Ryukyus, Okinawa, Japan

    T Tomoyose

  11. Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan

    M Onizuka

  12. Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan,

    M Takanashi

  13. Department of Hematology and Oncology, Hiroshima University Hospital, Hiroshima, Japan

    T Ichinohe

  14. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan,

    Y Atsuta

  15. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Y Atsuta

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  1. H Fujiwara
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ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation

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Correspondence to H Fujiwara.

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Fujiwara, H., Fuji, S., Wake, A. et al. Dismal outcome of allogeneic hematopoietic stem cell transplantation for relapsed adult T-cell leukemia/lymphoma, a Japanese nation-wide study. Bone Marrow Transplant 52, 484–488 (2017). https://doi.org/10.1038/bmt.2016.313

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