Nucleophosmin-1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3-internal tandem duplication (FLT3-ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT). We identified 1572 adult (age ≥ 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow-up for survivors was 23.7 months. FLT3-ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia-free survival (LFS) were negatively affected by concomitant FLT3-ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p < 0.0001, respectively), MRD positivity at transplant (HR 2.18, p < 10-5 and HR 1.71, p < 10-5 , respectively), and transplant in CR2 (HR 1.36, p = 0.026, and HR 1.26, p = 0.033, respectively), but positively affected by Karnofsky score ≥90 (HR 0.74, p = 0.012, and HR 0.7, p = 0.0002, respectively). Overall survival (OS) was also negatively influenced by concomitant FLT3-ITD (HR 1.6, p = 0.0001), MRD positivity at transplant (HR 1.61, p < 10-5 ), and older age (HR 1.22 per 10 years, p < 0.0001), but positively affected by matched sibling donor (unrelated donor: HR 1.35, p = 0.012; haploidentical donor: HR 1.45, p = 0.037) and Karnofsky score ≥90 (HR 0.73, p = 0.004). These results highlight the independent and significant role of FLT3-ITD, MRD status, and disease status on posttransplant outcomes in patients with NPM1-mutated AML allowing physicians to identify patients at risk of relapse who may benefit from posttransplant prophylactic interventions.

Centre Hospitalier Lyon Sud Service Hématologie Lyon France

CHRU BRABOIS Service Hématologie Vandoeuvre lès Nancy France

CHU de Lille Université de Lille Lille France

CHU Institut Universitaire du Cancer Toulouse Oncopole Toulouse France

Clinica Haematology Department Manchester Royal Infirmary Manchester UK

Department of Bone Marrow Transplantation University Hospital Essen Germany

Department of Haematology Cliniques Universitaires St Luc Brussels Belgium

Department of Hematology BMT Hôpital St Louis Paris France

Department of Hematology EBMT Paris Office CEREST TC Saint Antoine Hospital Paris France

Department of Hematology Gustave Roussy Cancer Campus BMT Service Villejuif France

Department of Hematology Oncology Charles University Hospital Pilsen Czech Republic

Department of Hematology University Medical Center Groningen University of Groningen Groningen The Netherlands

Department of Internal Medicine American University of Beirut Beirut Lebanon

Department of Internal Medicine Jacobi Medical Center Albert Einstein College of Medicine Bronx New York USA

Goethe Universitaet Medizinische Klinik 2 Hämatologie Medizinische Onkologie Frankfurt Germany

Hematology Division Chaim Sheba Medical Center Tel Hashomer Israel

Hôpital Jean Minjoz Service d`Hématologie Besançon France

HUCH Comprehensive Cancer Center Stem Cell Transplantation Unit Helsinki Finland

Programme de Transplantation and Therapie Cellulaire Centre de Recherche en Cancérologie de Marseille Marseille France

University Hospital Eppendorf Bone Marrow Transplantation Centre Hamburg Germany

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