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Clinical significance of total nucleated cell count in bone marrow of patients with acute lymphoblastic leukemia who underwent allogeneic hematopoietic stem cell transplantation

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Abstract

The clinical implications of recipient bone marrow nucleated cell count (NCC) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unknown. We conducted a multicenter retrospective study to evaluate the clinical significance of bone marrow NCC prior to allo-HSCT in patients with acute lymphoblastic leukemia. Patients who were in remission and underwent the initial allo-HSCT were included and stratified into high- and low-NCC groups using an NCC of 10 × 104/µL as the cut-off. The 3-year overall survival (OS), non-relapse mortality (NRM), and relapse rates for the high- and low-NCC groups were 51.2 vs. 84.5% (p < 0.001), 27.5 vs. 6.5% (p < 0.001), and 31.1 vs. 24.4% (p = 0.322), respectively. The high-NCC group had significantly poorer OS and higher NRM when compared with the low-NCC group. In summary, high recipient bone marrow NCC is associated with higher NRM and lower OS following allo-HSCT.

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Data availability

The data supporting the results of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank the medical staff at the Yokohama City University Medical Center, Yokohama City University School of Medicine, and Kanagawa Cancer Center for their excellent patient care.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Hematology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan

    Jun Nukui, Takayoshi Tachibana, Takuya Miyazaki, Masatsugu Tanaka, Kenji Matsumoto, Ayumi Numata, Taisei Suzuki, Akihiko Izumi, Natsuki Hirose & Heiwa Kanamori

  2. Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Jun Nukui, Kenji Matsumoto, Ayako Matsumura, Maki Hagihara & Hideaki Nakajima

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

    Takuya Miyazaki, Yoshimi Ishii, Yuki Nakajima & Shin Fujisawa

  4. Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan

    Koji Yamamoto

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  1. Jun Nukui
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Contributions

We gratefully acknowledge the contributions of all co-authors for data collection and analysis support. JN collected and analyzed data and wrote the manuscript. TT designed the study concept and comprehensively supported the study. TM collected data. MT and KY supported the statistical analysis. KM, YI, AN, YN, AM, TS, AI, and NH were the physicians for the patients. MH, SF, and HK were responsible for the participating centers. HN supervised the study. All authors critically revised the report, commented on drafts of the manuscript, and approved the final version of the manuscript.

Corresponding author

Correspondence to Takayoshi Tachibana.

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Conflicts of interest

All authors, except those mentioned below, declare no conflict of interest. TT reports honoraria from Pfizer, Otsuka, MSD, Chugai, Parma, and Astellas outside the submitted work. SF has received honoraria from Bristol-Myers-Squibb, Astellas, Nippon Shinyaku, Otsuka, Pfizer, Novartis, MSD, Sanofi, Janssen, SymBio, Kyowa Hakko Kirin, AstraZeneca, CSL Behring, Meiji Seika Pharma, AbbVie, Takeda, and Chugai Pharma, and received research funding from Shionogi, Kyowa Hakko Kirin, Chugai Pharma, Otsuka, Asahi-Kasei, and Daiichi Sankyo outside the submitted work. HN reports honoraria from Novartis and Daiichi-Sankyo, scholarships from Daiichi-Sankyo, Celgene, Chugai, Nihon-Shinyaku, Astellas, Asahi Kasei pharma, Takeda, Pfizer, and Eisai outside the submitted work.

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Supplementary Information

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12185_2023_3688_MOESM1_ESM.pptx

Supplementary Figure 1. A consort diagram of the patient selection. ALL, acute lymphoblastic leukemia; allo-HSCT, allogeneic hematopoietic stem cell transplantation; BM, bone marrow; NCC, nucleated cell count. Supplementary Figure 2. Receiver operating characteristic curve for the OS by NCC.OS, overall survival; NCC, nucleated cell count. Supplemental Figure 3. Correlations between NCC and sex (A), karyotype (B), and MRD (C). MRD, minimal residual disease; NCC, nucleated cell count. Supplemental Figure 4. The correlation between patient age and NCC; NCC, nucleated cell count. Supplemental Figure 5. Survival probability and cumulative incidence of relapse and NRM in Ph-negative and Ph-positive subgroups. Probability of OS in Ph-negative (A) and Ph-positive (B) subgroups, cumulative incidence of NRM in Ph-negative (C) and Ph-positive (D) subgroups, cumulative incidence of relapse in Ph-negative (E) and Ph-positive (F) subgroups. NRM, non-relapse mortality; OS, overall survival; Ph, Philadelphia

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Nukui, J., Tachibana, T., Miyazaki, T. et al. Clinical significance of total nucleated cell count in bone marrow of patients with acute lymphoblastic leukemia who underwent allogeneic hematopoietic stem cell transplantation. Int J Hematol 119, 62–70 (2024). https://doi.org/10.1007/s12185-023-03688-7

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