Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation.
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).
Klinikum Augsburg, Department of Hematology and Oncology, University of Munich, Augsburg, Germany;
Christoph
C
Schmid
Faculté de Médicine Saint-Antoine and European Group of Blood and Bone Marrow Transplantation (EBMT) Data Office, Paris, France;
Myriam
M
Labopin
Hopital St. Louis, Department of Hematology-Blood and Marrow Transplantation (BMT), Paris, France;
Gerard
G
Socié
Centre Hospitalier Regional Universitaire (CHRU) Besançon, Service d'Hématologie, Besançon, France;
Etienne
E
Daguindau
Helsinki University Hospital, Comprehensive Cancer Center, Stem Cell Transplantation Unit, Helsinki, Finland;
Liisa
L
Volin
Institut Universitaire du Cancer de Toulouse Oncopole, Hematology Department, Toulouse, France;
Anne
A
Huynh
Gustave Roussy, Institut de Cancérologie-BMT Service, Division of Hematology-Department of Medical Oncology, Villejuif, France;
Jean Henri
JH
Bourhis
Centre Hospitalier Universitaire (CHU) Bordeaux-Hôpital Haut-Leveque, Pessac, France;
Noel
N
Milpied
Erasmus MC-Daniel den Hoed Cancer Centre, Rotterdam, Netherlands;
Jan
J
Cornelissen
CHU Nantes-Department D'Hematologie, Nantes, France;
Patrice
P
Chevallier
University Hospital Gasthuisberg, Department of Hematology, Leuven, Belgium;
Johan
J
Maertens
Charles University Hospital-Department of Hematology/Oncology, Pilsen, Czech Republic;
Pavel
P
Jindra
Programme de Transplantation & Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille-Institut Paoli Calmettes, Marseille, France;
Didier
D
Blaise
University Hospital, Lund, Sweden;
Stig
S
Lenhoff
CHRU, Service des Maladies du Sang, Angers, France;
Norbert
N
Ifrah
Department of Medicine, Division of Hematology, University of Liège, Belgium;
Frédéric
F
Baron
Department of Hematology, Ospedale San Raffaele, Università degli Studi, Milano, Italy;
Fabio
F
Ciceri
Faculté de Médicine Saint-Antoine, Paris, France;
Claude
C
Gorin
Long-Term Transplant Clinic, Vanderbilt University Medical Center, Nashville, TN;
Bipin
B
Savani
Maria Sklodowska-Curie Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland;
Sebastian
S
Giebel
Faculté de Médicine Saint-Antoine and EBMT data office, Paris, France;
Emmanuelle
E
Polge
Department of Hematology, Hospital Clinic, Institut D'investigacions Biomediques August Pi y Sunyer, Barcelona, Spain;
Jordi
J
Esteve
Chaim Sheba Medical Center, Tel-Hashomer, Israel; and.
Arnon
A
Nagler
Faculté de Médicine Saint-Antoine and EBMT Data Office, Paris, France.
Mohamad
M
Mohty
D000328:Adult; D020732:Cytogenetic Analysis; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000090243:Nucleophosmin; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D020080:Tandem Repeat Sequences / Q000235:genetics*; D014184:Transplantation, Homologous; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C000716967:NPM1 protein, human; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3