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Impact of pretransplant central nervous system invasion in patients with aggressive adult T-cell leukemia lymphoma

Bone Marrow Transplantation volume 54, pages 134–137 (2019)Cite this article

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Adult T-cell leukemia–lymphoma (ATL) is one type of peripheral T-cell lymphoma caused by human T-cell lymphotrophic virus type I. Patients with aggressive ATL have dismal outcomes with intensive chemotherapy or anti-viral agents [1, 2]. In particular, once relapsed, most salvage chemotherapies are ineffective [3]. Thus, to improve the clinical outcome, up-front allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered in transplant-eligible patients [4, 5]. ATL patients often suffer from central nervous system (CNS) invasion [6, 7]. The impact of pre-transplant CNS invasion on the transplant outcome is unclear due to a limited number of report [8]. To clarify this issue, we retrospectively analyzed the impact of pre-transplant CNS invasion on the transplant outcome using a database of allo-HSCT recipients with ATL as previously reported [9]. This study was approved by the institutional review board of　the National Cancer Center, Tokyo, Japan. In this nationwide survey, we included patients who fulfilled the following criteria: 70 years old or younger, aggressive ATL (acute- and lymphoma-type ATL), diagnosis between 2000 and 2013, and receipt of intensive chemotherapy incorporating multiple chemotherapeutic drugs as first-line therapy. Out of this database, our current study included 961 allo-HSCT recipients with the information about the history of CNS invasion and its status at allo-HSCT. The OS rates were computed from the survival curves estimated by the Kaplan–Meier method. OS was defined as the time from allo-HSCT until death, with censoring on the last known alive date. A Cox proportional hazards regression model was used to analyze OS. The cumulative incidence of non-relapse mortality (NRM) was evaluated by the model of Fine and Gray for univariate and multivariate analyses. In the competing risk model for NRM, relapse was defined as a competing risk. NRM was defined as the time from allo-HSCT until death without relapse, and relapse was defined as the time from allo-HSCT until relapse, with censoring on the last known alive date. A two-sided P < 0.05 was considered statistically significant.

Our current retrospective study showed that a history of CNS invasion before allo-HSCT when CNS invasion is under control had no significant impact on the post-transplant clinical outcome. On the other hand, uncontrolled CNS invasion at allo-HSCT was associated with a dismal outcome after allo-HSCT as expected. Thus, when CNS invasion is controlled, a history of CNS invasion is not a contraindication of allo-HSCT. The impact of CNS invasion on the post-transplant outcome was comparable between MAC and RIC regimens. In terms of the impact of acute graft-versus-host disease on the outcome, there was no clear benefit of acute graft-versus-host disease in a landmark analysis or subgroup analysis of patients with a history of CNS invasion (data not shown). However, it might be due to a limited number of cases with a history of CNS invasion. In patients with uncontrolled CNS invasion, although the overall outcome was dismal, it was intriguing that a part of patients achieved a long-term survival even with uncontrolled CNS invasion. In order to further improve the outcome in such patients, novel treatment strategies including the modification of conditioning regimens, for instance use of thiotepa, should be explored. The limitations of this study should be clarified. We did not have any data about the effectiveness of each treatment for CNS invasion such as intrathecal chemotherapy, high-dose methotrexate, and radiation on the specific target organ including CNS. We did not have any data about the intrathecal chemotherapy either. Thus, it is unclear how we could treat patients with CNS invasion. In addition, we did not have any data whether ATL relapsed after allo-HSCT in CNS or in other sites after allo-HSCT. As reported in other hematological malignancies, there is a possibility that ATL is prone to relapse in CNS when there is a history of CNS invasion before allo-HSCT [10, 11].

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Acknowledgements

This research was partially supported by the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (15Ack0106136h0002) and the National Cancer Research and Development Fund (26-A-26).

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Authors and Affiliations

  1. Department of Hematology, Osaka International Cancer Institute, Osaka, Japan

    Shigeo Fuji

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

    Shigeo Fuji & Takahiro Fukuda

  3. Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan

    Yoshitaka Inoue

  4. Department of Hematology, Imamura General Hospital, Kagoshima, Japan

    Atae Utsunomiya

  5. Department of Hematology, Sasebo City General Hospital, Sasebo, Japan

    Yukiyoshi Moriuchi

  6. Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Ilseung Choi

  7. Department of Hematology, Oita Prefectural Hospital, Oita, Japan

    Eiichi Otsuka

  8. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Hideho Henzan

  9. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    Koji Kato

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

    Sawako Nakachi

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

    Hisashi Yamamoto

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  1. Shigeo Fuji
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Correspondence to Shigeo Fuji.

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Conflict of interest

SF received honoraria from Kyowa Hakko Kirin Co., Ltd.; AU received honoraria from Japan Blood Products Organization, Roche Diagnostics, Daiichi Sankyo, Siemens, Bristol-Myers Squibb, Pfizer, Astellas Pharma, Kyowa Hakko Kirin, Novartis Pharma, HUYA Bioscience International, Nippon Shinyaku, Chugai Pharma and Celgene, Immuno-Biological Laboratories, and Sumitomo Dainippon Pharma.

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Fuji, S., Inoue, Y., Utsunomiya, A. et al. Impact of pretransplant central nervous system invasion in patients with aggressive adult T-cell leukemia lymphoma. Bone Marrow Transplant 54, 134–137 (2019). https://doi.org/10.1038/s41409-018-0248-8

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