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Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT

Bone Marrow Transplantation volume 57, pages 562–571 (2022)Cite this article

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Abstract

Whether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy- Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23–4.24, p < 0.01; HR 2.65, 95% CI 1.46–4.81, p < 0.01, respectively). Haplo groups experienced a lower leukemia-free survival (LFS) compared to 1Ag-MMUD-PB (Haplo-BM: HR 1.51, 95% CI 1.06–2.14, p = 0.02; Haplo-PB: 1.47, 95% CI 1.05–2.05, p = 0.02); overall survival (OS) was also lower in Haplo-HCT (Haplo-BM: HR 1.50, 95% CI 1.02–2.21, p = 0.04; Haplo-PB: HR 1.51, 95% CI 1.05–2.19, p = 0.03). No differences were observed for graft-versus-host/relapse-free survival (GRFS) and relapse incidence (RI). Haplo-BM was associated with a lower risk of grade III-IV acute graft-versus-host disease (GVHD) (HR 0.44, 95% CI 0.24–0.81; p < 0.01), while no statistical differences were observed between groups for grade II-IV aGVHD and for cGVHD. Use of PTCy in 1Ag-MMUD-HCT is a valid alternative to consider when using alternative donors. Larger analysis of 1Ag-MMUD versus Haplo-HCT are warranted.

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Fig. 1: Non-relapse mortality and relapse incidence according to donor type and stem cell source.
Fig. 2: Overall survival, leukemia-free survival and graft-versus-host disease/relapse-free survival according to donor type and stem cell source.

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Acknowledgements

The authors thank Emmanuelle Polge from the office of the ALWP of the EBMT, and the clinical staff and investigators involved in this research. They especially thank the patients who took part.

Author information

Authors and Affiliations

  1. Federico II University of Naples, Hematology Department, Naples, Italy

    Giorgia Battipaglia & Fabrizio Pane

  2. Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy

    Giorgia Battipaglia & Fabrizio Pane

  3. EBMT Statistical Unit, Paris, France

    Jacques-Emmanuel Galimard, Myriam Labopin, Arnon Nagler & Mohamad Mohty

  4. Hematology Department, Hôpital Saint Antoine, Service d’Hématologie Thérapie Cellulaire, Paris, France

    Myriam Labopin & Mohamad Mohty

  5. Sorbonne Universités, UPMC Univ Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France

    Myriam Labopin & Mohamad Mohty

  6. UOC Ematologia e Trapianto di Midollo Osseo, IRCCS Ospedale Policlinico San Martino Genova, Genova, Italy

    Anna Maria Raiola

  7. Programme de Transplantation & Therapie Cellulaire, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, INSERM, CRCM, Marseille, France

    Didier Blaise

  8. Ospedale San Raffaele s.r.l., Haematology and BMT, Milano, Italy

    Annalisa Ruggeri & Fabio Ciceri

  9. Medicana International, Istanbul, Turkey

    Yener Koc

  10. Anadolu Medical Center Hospital, Bone Marrow Transplantation Department, Kocaeli, Turkey

    Zafer Gülbas

  11. Hematology Service, Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    Antonin Vitek

  12. Fondazione Policlinico A. Gemelli IRCCS, Roma, Italy; Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy

    Simona Sica

  13. Hematology department, Hospital General Universitario Gregorio Marañon, Instituto de Investigación Sanitaria Gregorio Marañon, Universidad Complutense Medicina, Madrid, Spain

    Jose Luiz Diez-Martin

  14. IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

    Luca Castagna

  15. SSCVD Trapianto di Cellule Staminali, AOU Città della Salute e della Scienza di Torino, Turin, Italy

    Benedetto Bruno

  16. Hospital Clinic, BMT Unit, Dept. of Hematology, IDIBAPS, Institut Josep Carreras, Barcelona, Spain

    Montserrat Rovira

  17. R.M. Gorbacheva Research Institute, Pavlov University, Saint Petersburg, Russian Federation

    Ivan Moiseev

  18. Division of Stem Cell Transplantation and Cellular Therapies, Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”, Reggio Calabria, Italy

    Massimo Martino

  19. ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA, Hematology Department, Milano, Italy

    Giovanni Grillo

  20. Hospital U. Marqués de Valdecilla, Servicio de Hematología-Hemoterapia, Santander, Spain

    Mercedes Colorado Araujo

  21. CHU Grenoble Alpes - Université Grenoble Alpes, Service d’Hématologie, Grenoble, France

    Claude Eric Bulabois

  22. Universite Paris IV, Hopital la Pitié-Salpêtrière, Hematologie Clinique, Paris, France

    Stéphanie Nguyen

  23. Hopital St. Louis, Dept. of Hematology - BMT, Paris, France

    Gerard Socié

  24. Florence Nightingale Sisli Hospital, Hematopoietic SCT Unit, Istanbul, Turkey

    Mutlu Arat

  25. Imperial College, Department of Haematology, Hammersmith Hospital, London, United Kingdom

    Jiri Pavlu

  26. Klinikum Grosshadern, Med. Klinik III, Munich, GermanyKlinikum Grosshadern, Med. Klinik III, Munich, Germany

    Johanna Tischer

  27. Goethe-Universitaet, Medizinische Klinik II, Hämatologie, Medizinische Onkologie, Frankfurt-Main, Germany

    Hans Martin

  28. Hematology Department, Complejo Asistencial Universitario de Salamanca-IBSAL; Centro de Investigación del Cáncer-IBMCC, Salamanca, Spain

    Lucia Lopez Corral

  29. University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Goda Choi

  30. CHU Bordeaux, Hôpital Haut-leveque, Pessac, France

    Edouard Forcade

  31. Alberts Cellular Therapy, Netcare Pretoria East Hospital, Pretoria, South Africa

    Andrew McDonald

  32. Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Ali Bazarbachi

  33. Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Arnon Nagler

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  1. Giorgia Battipaglia
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Contributions

GB designed the study and wrote the manuscript, JEG performed the statistical analysis. ML, FC, AN AR, and MMo revised the manuscript and all the authors reviewed and accepted its final version. AMR, DB, AR, YK, ZG, AV, SS, JLDM, LC, BB, MR, IM, MM, GG, MCA, CEB, SN, GS, MA, JP, JT, HM, LLC, GC, EF, AMD, FP, and AB were the principal investigators at the centers recruiting the highest number of patients for the study.

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Correspondence to Giorgia Battipaglia.

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Battipaglia, G., Galimard, JE., Labopin, M. et al. Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant 57, 562–571 (2022). https://doi.org/10.1038/s41409-022-01577-x

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