The association of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects after allogeneic stem-cell transplantation (SCT) is well-established but was not confirmed in the modern era and following post-transplant cyclophosphamide (PTCy). We assessed GVHD/ GVL association in AML patients following HLA-matched SCT with standard calcineurin-based (n = 12,653, 57% with additional in-vivo T-cell depletion) or PTCy-based (n = 508) GVHD prophylaxis. Following standard prophylaxis, acute GVHD grade II-IV and III-IV, chronic GVHD, and extensive chronic GVHD rates were 23.8%, 7.5%, 37.0%, and 16.3%, respectively. Acute GVHD grade II and III-IV were associated with lower relapse [hazard-ratio (HR) 0.85, P = 0.002; HR 0.76, P = 0.003, respectively)], higher non-relapse mortality (NRM) (HR 1.5, P < 0.001; HR 6.21, P < 0.001) and lower overall survival (OS) (HR 1.49, P < 0.001; HR 6.1, P < 0.001). Extensive chronic GVHD predicted lower relapse (HR 0.69, P < 0.001), higher NRM (HR 2.83, P < 0.001), and lower OS (HR 2.74, P < 0.001). Following PTCy, GVHD rates were 22.8%, 6.2%, 35.5%, and 17.7%, respectively. Acute GVHD was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001). Chronic GVHD was not prognostic for these outcomes. In conclusion, GVHD and GVL are strongly associated with contemporary SCT. However, following PTCy, GVHD is not associated with reduced relapse.

Clatterbridge Cancer Centre Liverpool Royal Liverpool University Hospital Clatterbridge Cancer Centre NHS Foundation Trust Division of Stem Cell Transplantation and Haemato Liverpool United Kingdom

Division of Hematology Chaim Sheba Medical Center Tel Hashomer and Tel Aviv University Tel Aviv Israel

Erasmus MC Cancer Institute University Medical Center Rotterdam Department of Hematology Rotterdam The Netherlands

Gorbacheva Research Institute Pavlov University St Petersburg Russia

Hématologie Clinique et Thérapie Cellulaire Hôpital Saint Antoine Paris France

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

Hospital Clinic Institute of Hematology and Oncology Dept of Hematology Barcelona Spain

Hospital Clínico de Valencia Servicio de Hematología Valencia Spain

Hospital Gregorio Marañón Sección de Trasplante de Medula Osea Madrid Spain

Institute of Hematology and Blood Transfusion Servicio de Hematología Prague Czech Republic

Medicana International Hospital Istanbul Bone Marrow Transplant Unit Istanbul Turkey

Sorbonne University INSERM UMRs 938 Paris France

Universita Cattolica S Cuore Istituto di Ematologia Ematologia Rome Italy

University Hospital Eppendorf Bone Marrow Transplantation Centre Hamburg Germany

University Hospital La Fe Hematology Department Valencia Spain

University Hospital Maastricht Dept Internal Med Hematology Oncology Maastricht The Netherlands

University Medical Center Groningen Dept of Hematology Groningen The Netherlands

VU University Medical Center Department of Hematology Amsterdam The Netherlands

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