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The association of graft-versus-leukemia effect and graft-versus host disease in haploidentical transplantation with post-transplant cyclophosphamide for AML

Bone Marrow Transplantation volume 57, pages 384–390 (2022)Cite this article

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Abstract

The association of graft-versus-host disease (GVHD) and graft-versus-leukemia effect after stem-cell transplantation (SCT) is well established but with limited data in the setting of haploidentical SCT (haploSCT) with post-transplant cyclophosphamide (PTCy). We used a series of landmark analyses to investigate this association in 805 AML patients following haploSCT. On day +100, 707 patients were alive and leukemia-free, 500 had no prior acute GVHD, 137 had acute GVHD grade II and 70 had grade III–IV. Subsequent relapse rates were 20.3%, 23.2% and 15.0%, respectively (P = 0.52). Subsequent non-relapse mortality (NRM) was 8.6%, 17.8% and 38.6%, respectively (P < 0.0001). Leukemia-free survival (LFS) was 71.0%, 59.0% and 46.3%, respectively (P < 0.0001). Multivariate analysis showed that acute GVHD grade II and grade III–IV were not associated with relapse (HR 1.21, P = 0.37 and HR 1.03, P = 0.94), but were associated with increased NRM (HR 2.09, P = 0.005 and HR 6.41, P < 0.0001) and lower LFS (HR 1.47, P = 0.02 and HR 2.59, P = < 0.0001). Chronic GVHD was not associated with subsequent relapse. Extensive chronic GVHD was associated with higher NRM (HR 6.72, P < 0.0001) and inferior LFS (HR 3.29, P = < 0.0001). GVHD of any type or grade is not associated with lower relapse after haploSCT with PTCy. Severe forms are associated with higher NRM and lower survival.

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Fig. 1: Transplantation outcomes after haploidentical transplantation.
Fig. 2: Transplantation outcomes after haploidentical transplantation.

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Acknowledgements

The authors acknowledge the contribution of all the EBMT centers contributing patients to this study.

Author information

Authors and Affiliations

  1. Division of Hematology, Chaim Sheba Medical Center, Tel-Hashomer and Sackler Medical School Tel-Aviv University, Tel-Aviv, Israel

    Avichai Shimoni & Arnon Nagler

  2. Sorbonne University, INSERM UMRs 938, Paris, France

    Myriam Labopin, Mohamad Mohty & Arnon Nagler

  3. Ospedale San Martino, Department of Haematology II, Genova, Italy

    Emanuele Angelucci

  4. Programme de Transplantation&Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France

    Didier Blaise

  5. Hematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, Milan, Italy

    Fabio Ciceri

  6. Medicana International, Istanbul, Turkey

    Yener Koc

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

    Zafer Gülbas

  8. Hospital Gregorio Marañón, Sección de Trasplante de Medula Osea, Madrid, Spain

    J. L. Diez-Martin

  9. S.C.V.D Trapianto di Cellule Staminali A.O.U Citta della Salute e della Scienza di Torino, Torino, Italy

    Benedetto Bruno

  10. Department of Oncology and Haematology, Istituto Clinico Humanitas, Transplantation Unit, Milano, Italy

    Luca Castagna

  11. Grande Ospedale Metropolitano Bianchi Melacrino Morelli - Centro Unico Trapianti Alberto Neri, Reggio Calabria, Italy

    Massimo Martino

  12. Department of Hematology, Hospital Clinic, Institute of Hematology & Oncology, Barcelona, Spain

    Montserrat Rovira

  13. Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France

    Mohamad Mohty

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  1. Avichai Shimoni
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Contributions

AS, ML, MM and AN, designed the research, analyzed and interpreted data, and wrote the manuscript; AS, ML, EA, DB, FC, YK, ZG, DMJL, BB, LC, MM, MR, MM and AN provided patients, collected and analyzed data, and critically reviewed the manuscript before submission. All authors read and approved the final manuscript.

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Correspondence to Avichai Shimoni.

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Shimoni, A., Labopin, M., Angelucci, E. et al. The association of graft-versus-leukemia effect and graft-versus host disease in haploidentical transplantation with post-transplant cyclophosphamide for AML. Bone Marrow Transplant 57, 384–390 (2022). https://doi.org/10.1038/s41409-021-01493-6

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