We retrospectively analyzed the impact of conditioning intensity on transplant outcomes according to their cytogenetic/molecular risk in a cohort of 1823 patients with acute myeloid leukemia (AML) and intermediate- or adverse-risk cytogenetics in first complete remission (CR1). These patients received their first hematopoietic stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCy). The intermediate-risk cytogenetic group included 1386 (76%) patients, and 608 (34%) had mutated FLT3-ITD. Myeloablative conditioning was used in 930 patients (51%), while 1130 (62%) received an intensified conditioning (score ≥2.5) based on the transplant conditioning intensity (TCI) score. Conditioning intensity using the myeloablative/reduced intensity stratification did not impact transplant outcomes across the entire cohort. However, a higher TCI score was associated with a lower risk of relapse, with no effect on survival. In specific cytogenetic risk groups, a higher TCI score did not influence outcomes in the adverse-risk group. In the intermediate-risk group, the impact varied with FLT3-ITD status. Patients with FLT3-ITD mutation who received a higher TCI showed a beneficial effect on relapse, leukemia-free survival (LFS), and overall survival. Conversely, in FLT3-ITD wild-type patients, more intense conditioning had a detrimental effect on graft-versus-host disease-free, and relapse-free survival with no effect on other outcomes. In conclusion, for AML patients in CR1 undergoing HSCT with PTCy, it is crucial to consider cytogenetic risk and molecular status when selecting the conditioning regimen. Intensive conditioning should be considered for patients with intermediate-risk cytogenetics and mutated FLT3-ITD but should probably be avoided for those with wild-type FLT3-ITD.

BMT Unit Department of Haematology Institute of Haematology and Oncology IDIBAPS Hospital Clinic University of Barcelona Josep Carreras Leukaemia Research Foundation Barcelona Spain

Centre Hospitalier Lyon Sud Lyon France

CHU Nantes Nantes France

Dél pesti Centrumkórház Budapest Hungary

EBMT Paris Office Hospital Saint Antoine Paris France

Erasmus MC Cancer Institute Rotterdam The Netherlands

Hannover Medical School Hannover Germany

Hematology and Bone Marrow transplant Unit San Raffaele Scientific Institute IRCCS Milano Italy

Hematology BMT and Institute of Cellular Therapy University of Patras Patras Greece

Hematology Department Hospital Universitari i Politècnic La Fe Valencia Departament de Medicina Universitat de Valencia CIBERONC Instituto Carlos 3 Madrid Spain

Hôpital Saint Antoine Sorbonne University INSERM UMRs 938 Paris France

Hospital Gregorio Marañón Madrid Spain

Institute of Hematology and Blood Transfusion Prague Czech Republic

Leiden University Medical Center Leiden The Netherlands

Programme de Transplantation and Therapie Cellulaire Marseille Marseille France

University Hospital Maastricht Maastricht The Netherlands

Vita Salute San Raffaele University Milano Italy

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