Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Effect of graft cell dose on second transplantation from a haploidentical donor with post-transplantation cyclophosphamide for relapsed/refractory acute leukemia

Bone Marrow Transplantation volume 58, pages 947–949 (2023)Cite this article

Subjects

Second allogeneic hematopoietic stem cell transplantation (allo-HCT2) is a potentially curative strategy for relapsed acute leukemia after first allo-HCT (allo-HCT1). Recent retrospective studies demonstrated that T-cell replete HLA-haploidentical hematopoietic cell transplantation with post-transplantation cyclophosphamide (PTCy-haplo) exhibited comparable efficacy and feasibility to conventional allo-HCT for patients with relapsed acute leukemia in allo-HCT2 [1, 2]. These studies identified several prognostic factors, including duration of remission after allo-HCT1 and disease status at allo-HCT2. The numbers of infused total nucleated cells (TNCs), CD34+, and CD3+ cells are also of interest because they can affect transplant outcomes. However, their effects on allo-HCT2 with PTCy-haplo have not yet been evaluated.

Between January 2007 and August 2020, we retrospectively analyzed consecutive patients aged 16 years or older at our institution who underwent allo-HCT2 with PTCy-haplo using peripheral blood stem cells (PBSCs) for relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) after allo-HCT1. Patients who received a second allograft for primary or secondary graft failure were excluded. Details of transplant procedures, definitions, and statistical analysis are provided in the Supplementary Methods. The study protocol was approved by the Ethics Committee of the Osaka Metropolitan University Graduate School of Medicine in accordance with the Declaration of Helsinki.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Survival outcomes according to CD34+ cell dose.

Data availability

The dataset analyzed in the current study is available from the corresponding author on reasonable request.

References

  1. Kharfan-Dabaja MA, Labopin M, Bazarbachi A, Ciceri F, Finke J, Bruno B, et al. Comparing outcomes of a second allogeneic hematopoietic cell transplant using HLA-matched unrelated versus T-cell replete haploidentical donors in relapsed acute lymphoblastic leukemia: a study of the Acute Leukemia Working Party of EBMT. Bone Marrow Transpl. 2021;56:2194–202.

    Article  CAS  Google Scholar 

  2. Kharfan-Dabaja MA, Labopin M, Brissot E, Kroger N, Finke J, Ciceri F, et al. Second allogeneic haematopoietic cell transplantation using HLA-matched unrelated versus T-cell replete haploidentical donor and survival in relapsed acute myeloid leukaemia. Br J Haematol. 2021;193:592–601.

    Article  CAS  PubMed  Google Scholar 

  3. Maffini E, Labopin M, Blaise D, Ciceri F, Gulbas Z, Deconinck E, et al. CD34+ cell dose effects on clinical outcomes after T-cell replete haploidentical allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia using peripheral blood stem cells. A study from the acute leukemia working Party of the European Society for blood and marrow transplantation (EBMT). Am J Hematol. 2020;95:892–9.

    Article  CAS  PubMed  Google Scholar 

  4. Yokoyama Y, Maie K, Fukuda T, Uchida N, Mukae J, Sawa M, 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 Transpl. 2020;55:1726–35.

    Article  CAS  Google Scholar 

  5. Elmariah H, Naqvi SMH, Kim J, Nishihori T, Mishra A, Perez L, et al. Impact of infused CD34+ stem cell dosing for allogeneic peripheral blood stem cell transplantation with post-transplant cyclophosphamide. Bone Marrow Transpl. 2021;56:1683–90.

    Article  CAS  Google Scholar 

  6. Gauntner TD, Brunstein CG, Cao Q, Weisdorf D, Warlick ED, Jurdi NE, et al. Association of CD34 cell dose with 5-year overall survival after peripheral blood allogeneic hematopoietic cell transplantation in adults with hematologic malignancies. Transplant Cell Ther. 2022;28:88–95.

    Article  CAS  PubMed  Google Scholar 

  7. Martin PS, Li S, Nikiforow S, Alyea EP 3rd, Antin JH, Armand P, et al. Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34+ cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation. Haematologica. 2016;101:499–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Collignon A, Calmels B, Harbi S, Furst S, Granata A, Faucher C, et al. Impact of CD34-positive cell dose on outcome after peripheral blood stem cell allogeneic transplantation prepared with ATG-based reduced intensity conditioning regimen. Am J Hematol. 2017;92:E57–E9.

    Article  PubMed  Google Scholar 

  9. Garnier A, Guillaume T, Peterlin P, Le Bourgeois A, Mahe B, Dubruille V, et al. Absence of influence of peripheral blood CD34+ and CD3+ graft cell counts on outcomes after reduced-intensity conditioning transplantation using post-transplant cyclophosphamide. Ann Hematol. 2020;99:1341–50.

    Article  CAS  PubMed  Google Scholar 

  10. Singh AK, Savani BN, Albert PS, Barrett AJ. Efficacy of CD34+ stem cell dose in patients undergoing allogeneic peripheral blood stem cell transplantation after total body irradiation. Biol Blood Marrow Transpl. 2007;13:339–44.

    Article  Google Scholar 

  11. Nakamae H, Okamura H, Hirose A, Koh H, Nakashima Y, Nakamae M, et al. A prospective study of an HLA-haploidentical peripheral blood stem cell transplantation regimen based on modification of the dose of posttransplant cyclophosphamide for poor prognosis or refractory hematological malignancies. Cell Transpl. 2022;31:9636897221112098.

    Article  Google Scholar 

  12. McCurdy SR, Kanakry CG, Tsai HL, Kasamon YL, Showel MM, Bolanos-Meade J, et al. Grade II acute graft-versus-host disease and higher nucleated cell graft dose improve progression-free survival after HLA-haploidentical transplant with post-transplant cyclophosphamide. Biol Blood Marrow Transpl. 2018;24:343–52.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the Japan Society for the Promotion of Science (JSPS; KAKENHI Grant number 20K07788).

Author information

Authors and Affiliations

  1. Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Yosuke Nakaya, Hirohisa Nakamae, Naonori Harada, Hiroshi Okamura, Kazuki Sakatoku, Kentaro Ido, Yosuke Makuuchi, Masatomo Kuno, Teruhito Takakuwa, Asao Hirose, Mika Nakamae, Mitsutaka Nishimoto, Yasuhiro Nakashima, Hideo Koh & Masayuki Hino

  2. Department of Hematology, Fuchu Hospital, Osaka, Japan

    Naonori Harada

  3. Department of Laboratory Medicine and Medical Informatics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Mika Nakamae

  4. Department of Preventive Medicine and Environmental Health, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Hideo Koh

Authors
  1. Yosuke Nakaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hirohisa Nakamae
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naonori Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroshi Okamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuki Sakatoku
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kentaro Ido
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yosuke Makuuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masatomo Kuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Teruhito Takakuwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Asao Hirose
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mika Nakamae
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mitsutaka Nishimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yasuhiro Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Hideo Koh
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Masayuki Hino
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YN (Nakaya) and HN conceptualized the study, analyzed data, and drafted the original manuscript. NH and HO interpreted the results and assisted in the statistical analysis. KS, KI, YM, MK, TT, AH, MN (Nakamae), MN (Nishimoto), YN (Nakashima), HK, and MH interpreted the results, and critically reviewed and revised the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Hirohisa Nakamae.

Ethics declarations

Competing interests

HN received research funding from Takeda Pharmaceutical Co., Ltd., and honoraria from Nippon Shinyaku Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Astellas Pharma Inc., and Takeda Pharmaceutical Co., Ltd. HO received research funding from Takeda Pharmaceutical Co., Ltd., and honoraria from Nippon Shinyaku Co., Ltd. TT received research funding from Pfizer Japan Inc., and honoraria from Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., and Takeda Pharmaceutical Co., Ltd. MN (Nishimoto) received research funding from Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and honoraria from Nippon Shinyaku Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., and Takeda Pharmaceutical Co., Ltd. YN (Nakashima) received research funding from Chugai Pharmaceutical Co., Ltd., Astellas Pharma Inc., and honoraria from Chugai Pharmaceutical Co., Ltd. and Kyowa Kirin Co., Ltd. HK received research funding from Takeda Pharmaceutical Co., Ltd., and honoraria from Takeda Pharmaceutical Co., Ltd. MH received research funding from Nippon Shinyaku Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., and honoraria from Sanofi K.K., Nippon Shinyaku Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Pfizer Japan Inc., Astellas Pharma Inc., and Takeda Pharmaceutical Co., Ltd.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakaya, Y., Nakamae, H., Harada, N. et al. Effect of graft cell dose on second transplantation from a haploidentical donor with post-transplantation cyclophosphamide for relapsed/refractory acute leukemia. Bone Marrow Transplant 58, 947–949 (2023). https://doi.org/10.1038/s41409-023-01986-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-023-01986-6

Search

Advanced search

Quick links