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Reduced post-transplant cyclophosphamide dose with antithymocyte globulin in peripheral blood stem cell haploidentical transplantation

Bone Marrow Transplantation volume 58, pages 1215–1222 (2023)Cite this article

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Abstract

Post-transplant cyclophosphamide (PT-Cy) is effective for graft-versus-host disease (GVHD) prophylaxis, but it may cause dose-dependent toxicities, particularly in frail patients. Therefore, we compared the outcomes with a reduced PT-Cy total dose (70 mg/kg) to those with the standard PT-Cy dose (100 mg/kg) in haploidentical hematopoietic cell transplantation (HCT) patients aged ≥ 65 years and those with cardiac comorbidities. All consecutive patients with a hematological malignancy receiving peripheral blood stem cells (PBSCs) after a thiotepa-based conditioning with low-dose antithymocyte globulin were included. Thirty-three patients received PT-Cy at 70 mg/kg and 25 at 100 mg/kg. PT-Cy dose reduction did not increase the risk of GVHD and was associated with faster neutrophil and platelet recovery, and lower cumulative incidences of bacteremia (38% versus 72%, p = 0.004) and cardiac complications (12% versus 44%, p = 0.028). At 2 years, GVHD-free, relapse-free survival (GRFS) was higher with the reduced dose compared to the standard dose (60% versus 33%, p = 0.04). In conclusion, reducing PT-Cy total dose to 70 mg/kg is a safe and valid approach for elderly patients and those with cardiac comorbidities underdoing haploidentical HCT with PBSCs and low-dose antithymocyte globulin. The reduced PT-Cy dose was associated with improved hematological count recovery, lower incidence of toxicities, and higher GRFS.

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Fig. 1: GRFS according to the total dose of PT-Cy.

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Data availability

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

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Acknowledgements

We thank all the clinicians, the nursing staff, and all the supportive care team for providing excellent care for our patients.

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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, Florent Malard, Eolia Brissot, Anne Banet, Simona Sestili, Ramdane Belhocine, Martina Calabro, Zoé Van de Wyngaert, Agnès Bonnin, Tounes Ledraa, Ollivier Legrand, Myriam Labopin & Mohamad Mohty

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

    Rémy Duléry, Florent Malard, Eolia Brissot, Ollivier Legrand & Mohamad Mohty

  3. Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation (EBMT) Paris Study Office/CEREST-TC, Paris, France

    Myriam Labopin

  4. Sorbonne University, UNICO—GRECO Cardio Oncology Program, Saint-Antoine Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France

    Elodie Capderou, Ariel Cohen & Stéphane Ederhy

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Contributions

RD designed the study, recruited patients, collected, assembled, and analyzed data, performed the statistical analysis, and wrote the manuscript. MM designed the study, supervised research, analyzed data, and commented on the manuscript. SE, AC, and EC helped design the study, performed cardiac evaluations of the patients, analyzed data, and commented on the manuscript. ML analyzed data, performed the statistical analysis, and commented on the manuscript. AB and TL contributed to patient care and commented on the manuscript. FM, EB, AB, SS, RB, MC, ZVW, and OL recruited patients and commented on the manuscript. All authors reviewed the manuscript and approved its submission for publication purposes.

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Correspondence to Rémy Duléry.

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Duléry, R., Malard, F., Brissot, E. et al. Reduced post-transplant cyclophosphamide dose with antithymocyte globulin in peripheral blood stem cell haploidentical transplantation. Bone Marrow Transplant 58, 1215–1222 (2023). https://doi.org/10.1038/s41409-023-02085-2

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