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A high CD34+ cell dose is associated with better disease-free survival in patients with low-risk diseases undergoing peripheral blood stem cell transplantation from HLA-matched related donors

Bone Marrow Transplantation volume 55, pages 1726–1735 (2020)Cite this article

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Abstract

To elucidate the impact of infused CD34+ cell doses on transplant outcome, we retrospectively analyzed 851 adult patients who received peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen (HLA)-matched related donors. The patients were divided into high- and low-CD34 groups at the cutoff value of 4.5 × 106/kg. Overall, the high CD34 group showed early neutrophil and platelet recovery. Stratification of disease risks demonstrated that among the patients with low-risk diseases, the high-CD34 group showed better disease-free survival (DFS) (64.9% vs. 55.5%, P = 0.0415) than did the low-CD34 group, without any increase in graft-versus-host disease (GVHD). Meanwhile, a higher CD34+ cell dose had no impacts on the outcomes of patients with high-risk diseases. Multivariate analyses for the patients with low-risk diseases revealed that a high CD34+ cell dose (hazard ratio [HR] 0.72, P = 0.048) and development of grade III-to-IV acute GVHD (HR 1.64, P = 0.018) were significantly associated with DFS. An excessive dose of CD34+ cells (>8.0 × 106/kg) led to an increase in acute GVHD. By stratification of disease risk, a CD34+ cell dose between 4.5 and 8.0 × 106/kg can be suggested for patients with low-risk diseases who undergo PBSCT from HLA-matched related donors.

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Fig. 1
Fig. 2: Disease-free and overall survival.
Fig. 3: Cumulative incidences of relapse, nonrelapse mortality, and graft-versus-host disease (GVHD) in patients with low-risk diseases.

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Acknowledgements

We thank the all the staff members of the collaborating institutes of the Japan Society for Hematopoietic Cell Transplantation. We appreciate Flaminia Miyamasu for English proofreading.

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Author notes

  1. These authors contributed equally: Yasuhisa Yokoyama, Koichiro Maie

Authors and Affiliations

  1. Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

    Yasuhisa Yokoyama, Koichiro Maie & Shigeru Chiba

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

    Takahiro Fukuda

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

    Naoyuki Uchida

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

    Junichi Mukae

  5. Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan

    Masashi Sawa

  6. Department of Hematology, Aomori Prefectural Central Hospital, Aomori, Japan

    Kohmei Kubo

  7. Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Tokyo, Japan

    Mineo Kurokawa

  8. Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Hirohisa Nakamae

  9. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Tatsuo Ichinohe

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

    Yoshiko Atsuta

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

    Yoshiko Atsuta

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  1. Yasuhisa Yokoyama
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Correspondence to Shigeru Chiba.

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Conflict of interest

MK reports grants from Astellas Pharma Inc., grants from MSD KK, Eisai Co., Ltd, Otsuka Pharmaceutical Co., Ltd., ONO PHARMACEUTICAL CO., LTD, Takeda Pharmaceutical Company Limited., Chugai Pharmaceutical Company, Sumitomo Dainippon Pharma Co.,Ltd, Kyowa Hakko Kirin Co., Ltd, Nippon Shinyaku Co., Ltd, Bristol-Myers Squibb, Pfizer Japan Inc., Teijin Limited, TOYAMA CHEMICAL CO., LTD, and Novartis Pharma KK, and personal fees from Celgene KK and Shionogi & Co., Ltd, outside the submitted work.

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Yokoyama, Y., Maie, K., Fukuda, T. et al. A high CD34+ cell dose is associated with better disease-free survival in patients with low-risk diseases undergoing peripheral blood stem cell transplantation from HLA-matched related donors. Bone Marrow Transplant 55, 1726–1735 (2020). https://doi.org/10.1038/s41409-020-0817-5

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