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Reduced post-transplant cyclophosphamide doses in haploidentical hematopoietic cell transplantation for elderly patients with hematological malignancies

Bone Marrow Transplantation volume 58, pages 386–392 (2023)Cite this article

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Abstract

Although post-transplant cyclophosphamide (PT-Cy) is effective for graft-versus-host disease (GVHD) prophylaxis, it is associated with toxicities, which might be dose-dependent. We compared the outcomes with PT-Cy at 80 mg/kg to those with PT-Cy at 100 mg/kg in elderly patients undergoing haploidentical hematopoietic cell transplantation (HCT). Inclusion criteria included peripheral blood stem cells, hematological malignancy, and age>65 years (or age>60 years if cardiac event history). Thirty-eight patients received PT-Cy at 80 mg/kg and 55 100 mg/kg, divided in two doses. The cumulative incidences (CI) of acute grade II–IV, acute grade III–IV, and moderate/severe chronic GVHD were 32%, 16%, and 13% with PT-Cy at 80 mg/kg compared to 33%, 13%, and 16% with 100 mg/kg, respectively. In multivariable analysis, reducing PT-Cy dose had no significant impact on GVHD. Neutrophil and platelet engraftments were significantly improved, and CI of BK virus-associated hemorrhagic cystitis was reduced with 80 mg/kg of PT-Cy compared to 100 mg/kg. At 2 years, non-relapse mortality was 16% and 31%, progression-free survival 65% and 49%, overall survival 70% and 56%, and GVHD-free, relapse-free survival 52% and 36% with 80 mg/kg and 100 mg/kg, respectively. Reducing PT-Cy dose to 80 mg/kg is safe and associated with improved hematological recovery and lower CI of hemorrhagic cystitis in elderly patients undergoing haploidentical HCT.

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Fig. 1: Graft-versus-host disease.
Fig. 2: Survival outcomes.

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Data availability

The dataset supporting the conclusions of this article is available upon demand to the corresponding author.

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Acknowledgements

We thank all the clinicians, pharmacists, and the nursing staff for providing excellent care for our patients, especially Agnès Bonnin, Chiara De Philippis, Iacopo Mariotti, Barbara Sarina, and Armando Santoro.

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Authors and Affiliations

  1. Department of Clinical Hematology and Cellular Therapy, Sorbonne University, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France

    Rémy Duléry, Antonio Bianchessi, Florent Malard, Eolia Brissot, Simona Sestili, Anne Banet, Zoé Van de Wyngaert, Ramdane Belhocine & Mohamad Mohty

  2. INSERM UMRs 938, Centre de Recherche Saint-Antoine (CRSA), Paris, France

    Rémy Duléry, Florent Malard, Eolia Brissot, Anne Banet, Zoé Van de Wyngaert & Mohamad Mohty

  3. Transplant and Cellular Immunotherapy Program, Department of Hematology, Institut Paoli Calmettes, Marseille, France

    Claire Goudet, Angela Granata, Samia Harbi, Valerio Maisano, Didier Blaise, Sabine Fürst & Raynier Devillier

  4. Department of Hematology - Bone Marrow Transplant and Cell Therapy Unit, IRCSS Humanitas Clinical and Research Center, Milan, Italy

    Daniele Mannina & Stefania Bramanti

  5. Division of Hematology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

    Antonio Bianchessi

  6. Cell Therapy Unit, Institut Paoli Calmettes, Marseille, France

    Christian Chabannon & Didier Blaise

  7. Management Sport Cancer Laboratoire, Aix-Marseille University, Marseille, France

    Christian Chabannon, Didier Blaise & Raynier Devillier

  8. Department of Cardiology, UNICO – GRECO cardio oncology Program, Sorbonne University, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France

    Stéphane Ederhy

  9. Bone Marrow Unit, Ospedale Villa Sofia Cervello, Palermo, Italy

    Luca Castagna

Authors
  1. Rémy Duléry
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  2. Claire Goudet
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Contributions

R Duléry and R Devillier designed the study, collected, assembled, and analyzed data, performed statistical analysis, and wrote the manuscript. MM, DB, and SF designed the study, supervised research, analyzed data, and commented on the manuscript. CG, DM, and AB collected, assembled, and analyzed data, recruited patients, and commented on the manuscript. SE helped designing the study, analyzed data, and commented on the manuscript. AG, SH, VM, CC, FM, EB, SS, AB, ZVW, RB, LC, and SB recruited patients and commented the manuscript. All authors reviewed the manuscript and approved submission of the manuscript for publication purposes.

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Correspondence to Rémy Duléry.

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Duléry, R., Goudet, C., Mannina, D. et al. Reduced post-transplant cyclophosphamide doses in haploidentical hematopoietic cell transplantation for elderly patients with hematological malignancies. Bone Marrow Transplant 58, 386–392 (2023). https://doi.org/10.1038/s41409-022-01908-y

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