To analyze the influence of distinct combinations of molecular aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for cytogenetically normal acute myeloid leukemia (CN-AML), a retrospective registry analysis was performed on 702 adults undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1(mut)) and FLT3 internal tandem duplications (FLT3-ITD). Double-negative patients were evaluated for mutations of the CCAAT/enhancer binding protein α gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. Two-year OS from HSCT was 81 ± 5% in NPM1(mut)/FLT3(wt), 75 ± 3% in NPM1(wt)/FLT3(wt), 66 ± 3% in NPM1(mut)/FLT3-ITD, and 54 ± 7% in NPM1(wt)/FLT3-ITD (P = .003). Analysis of CEBPα among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBPα(mut) and with a triple negative genotype (2-year OS: 100%/77 ± 3%). In a Cox-model of predefined variables, age, FLT3-ITD and >1 course of chemotherapy to reach CR were risk factors associated with inferior outcome, regardless of NPM1 mutational status, variations of transplant protocols, or development of graft-versus-host disease. In a prognostic risk classification, 2-year OS/LFS rates were 88 ± 3%/79 ± 4% without any, 77 ± 2%/73 ± 3% with one, and 53 ± 4%/50 ± 4 with ≥2 risk factors (P = .003/.002).

Centre Hospitalier Regional Universitaire Besançon Service d'Hématologie Besançon France;

Centre Hospitalier Universitaire Bordeaux Hôpital Haut Leveque Pessac France;

Chaim Sheba Medical Center Tel Hashomer Israel; and

Charles University Hospital Department of Hematology Oncology Pilsen Czech Republic;

CHRU Service des Maladies du Sang Angers France;

CHU Nantes Department D'Hematologie Nantes France;

Department of Hematology Hospital Clinic Institut D'investigacions Biomediques August Pi y Sunyer Barcelona Spain;

Department of Hematology Ospedale San Raffaele Università degli Studi Milano Italy;

Department of Medicine Division of Hematology University of Liège Belgium;

Erasmus MC Daniel den Hoed Cancer Centre Rotterdam Netherlands;

Faculté de Médicine Saint Antoine and EBMT Data Office Paris France

Faculté de Médicine Saint Antoine and EBMT data office Paris France;

Faculté de Médicine Saint Antoine and European Group of Blood and Bone Marrow Transplantation Data Office Paris France;

Faculté de Médicine Saint Antoine Paris France;

Gustave Roussy Institut de Cancérologie BMT Service Division of Hematology Department of Medical Oncology Villejuif France;

Helsinki University Hospital Comprehensive Cancer Center Stem Cell Transplantation Unit Helsinki Finland;

Hopital St Louis Department of Hematology Blood and Marrow Transplantation Paris France;

Institut Universitaire du Cancer de Toulouse Oncopole Hematology Department Toulouse France;

Klinikum Augsburg Department of Hematology and Oncology University of Munich Augsburg Germany;

Long Term Transplant Clinic Vanderbilt University Medical Center Nashville TN;

Maria Sklodowska Curie Cancer Center and Institute of Oncology Gliwice Branch Gliwice Poland;

Programme de Transplantation and Therapie Cellulaire Centre de Recherche en Cancérologie de Marseille Institut Paoli Calmettes Marseille France;

University Hospital Gasthuisberg Department of Hematology Leuven Belgium;

University Hospital Lund Sweden;

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Comparison of HLA-mismatched unrelated donor transplantation with post-transplant cyclophosphamide versus HLA-haploidentical transplantation in patients with active acute myeloid leukemia

Measurable residual disease, FLT3-ITD mutation, and disease status have independent prognostic influence on outcome of allogeneic stem cell transplantation in NPM1-mutated acute myeloid leukemia