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Impact of donor-derived CD34 + infused cell dose on outcomes of patients undergoing allo-HCT following reduced intensity regimen for myelofibrosis: a study from the Chronic Malignancies Working Party of the EBMT

Bone Marrow Transplantation volume 57, pages 261–270 (2022)Cite this article

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Abstract

The optimal CD34 + cell dose in the setting of RIC allo-HCT for myelofibrosis (MF) remains unknown. We retrospectively analyzed 657 patients with primary or secondary MF transplanted with use of peripheral blood (PB) stem cells after fludarabine/melphalan or fludarabine/busulfan RIC regimen. Median patient age was 58 (range, 22–76) years. Donors were HLA-identical sibling (MSD) or unrelated (UD). Median follow-up was 46 (2–194) months. Patients transplanted with higher doses of CD34 + cells (>7.0 × 106/kg), had an increased chance of achievement of both neutrophil (hazard ratio (HR), 1.46; P < 0.001) and platelet engraftment (HR, 1.43; P < 0.001). In a model with interaction, for patients transplanted from a MSD, higher CD34 + dose was associated with improved overall survival (HR, 0.63; P = 0.04) and relapse-free survival (HR, 0.61; P = 0.02), lower risk of non-relapse mortality (HR, 0.57; P = 0.04) and higher rate of platelet engraftment. The combined effect of higher cell dose and UD was apparent only for higher neutrophil and platelet recovery rate. We did not document any detrimental effect of high CD34 + dose on transplant outcomes. More bulky splenomegaly was an adverse factor for survival, engraftment and NRM. Our analysis suggests a potential benefit for MF patients undergoing RIC PB-allo-HCT receiving more than 7.0 × 106/kg CD34 + cells.

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Fig. 1: AlloHCT outcomes according to CD34+ cell dose.
Fig. 2: AlloHCT outcomes according to donor type and CD34 + cell dose.

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Acknowledgements

The authors would like to thank all investigators and data managers in the EBMT participating centers for their contribution to this analysis. Detailed list is presented in Supplementary Appendix.

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Authors and Affiliations

  1. Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland

    Tomasz Czerw

  2. Department of Biology, Tor Vergata University, Rome, Italy

    Simona Iacobelli & Vittoria Malpassuti

  3. EBMT Data Office, Leiden, Netherlands

    Linda Koster

  4. University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

  5. Hopital Saint Louis, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France

    Marie Robin

  6. University Hospital Gasthuisberg, Leuven, Belgium

    Johan Maertens

  7. CHU Nantes, Nantes, France

    Patrice Chevallier

  8. Karolinska University Hospital, Stockholm, Sweden

    Emma Watz

  9. Cliniques Universitaires St. Luc, Brussels, Belgium

    Xavier Poiré

  10. Sheffield Teaching Hospitals NHS Trust, Sheffield, UK

    John A. Snowden

  11. University Medical Centre, Utrecht, Netherlands

    Jürgen Kuball

  12. University Hospital Birmingham NHS Trust, Birmingham, UK

    Francesca Kinsella

  13. Institut Paoli Calmettes, Marseille, France

    Didier Blaise

  14. Dél-pesti Centrumkórház, Budapest, Hungary

    Péter Reményi

  15. Centre Hospitalier Universitaire de Rennes, Rennes, France

    Jean-Baptiste Mear

  16. University Hospital, Linkoeping, Sweden

    Jörg Cammenga

  17. CHRU BRABOIS, Vandoeuvre Les Nancy, France

    Marie Thérèse Rubio

  18. Hôpital Henri Mondor, Creteil, France

    Sebastien Maury

  19. Hopital Jean Minjoz, Besancon, France

    Etienne Daguindau

  20. Belfast City Hospital, Belfast, UK

    Damian Finnegan

  21. Trinity College Dublin, St. James’s Hospital, Dublin, Ireland

    Patrick Hayden

  22. Hospital Clínico Universitario-INCLIVA, University of Valencia, Valencia, Spain

    Juan Carlos Hernández-Boluda

  23. Guys’ and St. Thomas’ NHS Foundation Trust and University College London Hospitals, London, UK

    Donal McLornan

  24. CHfU de Lille, Université de Lille, INSERM U1286, Infinite, 59000, Lille, France

    Ibrahim Yakoub-Agha

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Contributions

TC was the primary investigator for this study. TC, SI, VM, LC, PH, JCH-B, DM, and IY-A designed the study, the synopsis of which was approved by the Chronic Malignancies Working Party of the EBMT. SI, VM, and LC did the statistical analysis. TC wrote the first draft of the paper. All other co-authors contributed data to the EBMT registry, read the paper and approved the final version.

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Correspondence to Tomasz Czerw.

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Czerw, T., Iacobelli, S., Malpassuti, V. et al. Impact of donor-derived CD34 + infused cell dose on outcomes of patients undergoing allo-HCT following reduced intensity regimen for myelofibrosis: a study from the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transplant 57, 261–270 (2022). https://doi.org/10.1038/s41409-021-01540-2

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