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Minimal residual disease (MRD) positivity at allogeneic hematopoietic cell transplantation, not the quantity of MRD, is a risk factor for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia

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Abstract

Minimal residual disease (MRD) monitoring by quantitative real-time reverse transcription PCR (qRT-PCR) is the standard of care in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). We evaluated the impact of MRD status at hematopoietic cell transplantation (HCT) on relapse, as measured by a unified protocol at a central laboratory. Only patients with Ph-positive ALL who had minor transcripts (e1a2) and who underwent allogeneic HCT in first complete remission between 2008 and 2017 were included. First, patients with negative-MRD (n = 196) and positive-MRD (n = 61) at HCT were analyzed. As expected, MRD positivity at HCT was significantly associated with an increased risk of hematological relapse (hazard ratio [HR], 2.91; 95% CI 1.67–5.08; P < 0.001) in the multivariate analysis. Next, patients with positive-MRD were divided into low-MRD (n = 39) and high-MRD (n = 22) groups. In the multivariate analysis, high-MRD at HCT was not significantly associated with an increased risk of hematological relapse compared to the low-MRD group (HR 1.10; 95% CI 0.54–2.83; P = 0.620). These results indicate that the therapeutic decisions should be made based on MRD positivity, rather than on the MRD level, at HCT.

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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. We are grateful to the team of technicians in the RNA Analysis Section, Genetic and Pathology Department, SRL, Inc. for their excellent work. Y. Akahoshi is a Research Fellow of Japan Society of the Promotion of Science (JSPS) and this work was supported by JSPS KAKENHI Grant Number JP20J10298.

Author information

Authors and Affiliations

  1. Division of Hematology, Jichi Medical University Saitama Medical Center, 1-847 Amanuma-cho, Omiya-ku, Saitama city, Saitama, 330-8503, Japan

    Yu Akahoshi, Yoshinobu Kanda & Shinichi Kako

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

    Yasuyuki Arai

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

    Satoshi Nishiwaki

  4. Department of Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan

    Shuichi Mizuta

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

    Atsushi Marumo

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

    Naoyuki Uchida

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

    Yoshinobu Kanda

  8. Department of Hematology, Shinshu University, Matsumoto, Japan

    Hitoshi Sakai

  9. Department of Hematology, Saiseikai Maebashi Hospital, Maebashi, Japan

    Satoru Takada

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

    Takahiro Fukuda

  11. Department of Hematology, Yokohama City University Medical Center, Yokohama, Japan

    Shin Fujisawa

  12. Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University Hospital, Osakasayama, Japan

    Takashi Ashida

  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

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

    Yoshiko Atsuta

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  1. Yu Akahoshi
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  2. Yasuyuki Arai
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  15. Shinichi Kako
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Contributions

Y. Akahoshi designed the study, analyzed the data, and wrote the manuscript; Y. Arai, SN, SM, and SK reviewed and revised the manuscript; AM, NU, YK, HS, ST, TF, SF, TA, JT, and Y. Atsuta collected the patient data; all authors contributed to the writing of the report and approved the final version of the article.

Corresponding author

Correspondence to Shinichi Kako.

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Akahoshi, Y., Arai, Y., Nishiwaki, S. et al. Minimal residual disease (MRD) positivity at allogeneic hematopoietic cell transplantation, not the quantity of MRD, is a risk factor for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia. Int J Hematol 113, 832–839 (2021). https://doi.org/10.1007/s12185-021-03094-x

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