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Reduced-intensity conditioning is a reasonable alternative for Philadelphia chromosome-positive acute lymphoblastic leukemia among elderly patients who have achieved negative minimal residual disease: a report from the Adult Acute Lymphoblastic Leukemia Working Group of the JSHCT

Bone Marrow Transplantation volume 55, pages 1317–1325 (2020)Cite this article

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Abstract

Reduced-intensity conditioning (RIC) regimens have been widely used for allogeneic hematopoietic cell transplantation (HCT) in elderly patients. After the emergence of tyrosine kinase inhibitor (TKI), most patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) now achieve negative results for minimal residual disease (MRD) at HCT. In this study, we evaluated patients aged 50 years or more with Ph-positive ALL who received TKI before HCT, achieved negative-MRD at HCT, and underwent their first allogeneic HCT between 2008 and 2017. In total, 90 and 136 patients who received myeloablative conditioning (MAC) and a RIC regimen, respectively, were included. The median age of patients with MAC and RIC was 54 and 60 years, respectively. Even in multivariate analyses, RIC was not significantly associated with overall mortality (hazard ratio [HR], 1.09; P = 0.724), hematological relapse (HR, 1.97; P = 0.170), or non-relapse mortality (HR, 0.84; P = 0.540). Subgroup analyses suggested that RIC resulted in superior overall survival due to a lower incidence of non-relapse mortality in patients with a poor performance status or a high HCT comorbidity index. In conclusion, RIC is a reasonable option for elderly patients with negative-MRD at HCT.

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Fig. 1: Transplant outcomes in the MAC and RIC groups.
Fig. 2: Impact of the conditioning intensity on overall survival in groups stratified according to age at HCT, KPS, or HCT-CI score in multivariate analyses.

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Acknowledgements

The authors greatly appreciate the contributions of many physicians and data managers throughout the JSHCT, the Japan Marrow Donor Program (JMDP), and the Japan Cord Blood Bank Network (JCBBN), who made this analysis possible. We would also like to thank the members of the Transplant Registry Unified Management committees at JSHCT, JMDP, and JCBBN for their dedicated management of data.

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Authors and Affiliations

  1. Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

    Yu Akahoshi, Yoshinobu Kanda & Shinichi Kako

  2. Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan

    Satoshi Nishiwaki

  3. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Yasuyuki Arai

  4. Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan

    Kaito Harada

  5. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Yuho Najima

  6. Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan

    Yoshinobu Kanda

  7. Department of Hematology, Chiba Aoba Municipal Hospital, Chiba, Japan

    Katsuhiro Shono

  8. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Shuichi Ota

  9. Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

  10. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan

    Naoyuki Uchida

  11. Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan

    Souichi Shiratori

  12. Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan

    Masatsugu Tanaka

  13. Department of Hematology, Tokyo Women’s Medical University, Tokyo, Japan

    Junji Tanaka

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

    Yoshiko Atsuta

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  1. Yu Akahoshi
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Contributions

Y. Akahoshi designed the study, analyzed the data, and wrote the first draft of paper; SN, Y. Arai, KH, and SK reviewed, and revised the paper; YN, YK, KS, SO, TF, NU, SS, and MT provided important clinical data; J.T., and Y. Atsuta collected the patient data; All authors contributed to the writing of the report and approved the final version of the article.

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Correspondence to Shinichi Kako.

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Akahoshi, Y., Nishiwaki, S., Arai, Y. et al. Reduced-intensity conditioning is a reasonable alternative for Philadelphia chromosome-positive acute lymphoblastic leukemia among elderly patients who have achieved negative minimal residual disease: a report from the Adult Acute Lymphoblastic Leukemia Working Group of the JSHCT. Bone Marrow Transplant 55, 1317–1325 (2020). https://doi.org/10.1038/s41409-020-0951-0

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