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Newly proposed threshold and validation of white blood cell count at diagnosis for Philadelphia chromosome-positive acute lymphoblastic leukemia: risk assessment of relapse in patients with negative minimal residual disease at transplantation—a report from the Adult Acute Lymphoblastic Leukemia Working Group of the JSTCT

Bone Marrow Transplantation volume 56, pages 2842–2848 (2021)Cite this article

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Abstract

White blood cell count (WBC) at diagnosis is the conventional prognostic factor in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Nevertheless, little is known about the impact of WBC at diagnosis considering the minimal residual disease (MRD) status at allogeneic hematopoietic cell transplantation (HCT). We evaluated adult patients with Ph+ ALL who achieved negative-MRD and received HCT in first complete remission between 2006 and 2018. The entire cohort was temporally divided into derivation (n = 258) and validation cohorts (n  =  366). Using a threshold of 15,000/μL, which was determined by a receiver operating characteristic curve analysis in the derivation cohort, high WBC was associated with an increased risk of hematological relapse in both the derivation cohort (25.3% vs. 11.6% at 7 years, P = 0.004) and the validation cohort (16.2% vs. 8.5% at 3 years, P = 0.025). In multivariate analyses, high WBC was a strong predictor of hematological relapse in the derivation cohort (HR, 2.52, 95%CI 1.32–4.80, P = 0.005) and in the validation cohort (HR, 2.32, 95%CI, 1.18–4.55; P = 0.015). In conclusion, WBC at diagnosis with a new threshold of 15,000/μL should contribute to better risk stratification in patients with negative-MRD at HCT.

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Fig. 1: Early derivation cohort.
Fig. 2: Late validation cohort.
Fig. 3: Entire cohort.

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Acknowledgements

The authors greatly appreciate the contributions of many physicians and data managers throughout the JSTCT, 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 JSTCT, JMDP, and JCBBN for their dedicated management of data. 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.

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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 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, Kanagawa Cancer Center, Yokohama, Japan

    Takayoshi Tachibana & Masatsugu Tanaka

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

    Akihito Shinohara & Junji Tanaka

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

    Noriko Doki

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

    Naoyuki Uchida

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

    Yoshinobu Kanda

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

    Souichi Shiratori

  10. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Yukiyasu Ozawa

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

    Katsuhiro Shono

  12. Department of Hematology, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan

    Yuta Katayama

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

    Takahiro Fukuda

  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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Contributions

Y. Akahoshi. designed the study, analyzed the data, and wrote the manuscript; Y. Arai., S.N., T. T., A.S. and S.K. reviewed, and revised the manuscript; N.D., N.U., M.T., Y. Kanda., S.S., Y.O., K.S. and Y. Katayama. provided important clinical data; J.T., T.F. 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 Yu Akahoshi.

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Akahoshi, Y., Arai, Y., Nishiwaki, S. et al. Newly proposed threshold and validation of white blood cell count at diagnosis for Philadelphia chromosome-positive acute lymphoblastic leukemia: risk assessment of relapse in patients with negative minimal residual disease at transplantation—a report from the Adult Acute Lymphoblastic Leukemia Working Group of the JSTCT. Bone Marrow Transplant 56, 2842–2848 (2021). https://doi.org/10.1038/s41409-021-01422-7

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