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Outcome and risk factor analysis of molecular subgroups in cytogenetically normal AML treated by allogeneic transplantation.

In English

Författare

  • Christoph Schmid
  • Myriam Labopin
  • Gerard Socié
  • Etienne Daguindau
  • Liisa Volin
  • Anne Huynh
  • Jean Henri Bourhis
  • Noel Milpied
  • Jan Cornelissen
  • Patrice Chevallier
  • Johan Maertens
  • Pavel Jindra
  • Didier Blaise
  • Stig Lenhoff
  • Norbert Ifrah
  • Frédéric Baron
  • Fabio Ciceri
  • Claude Gorin
  • Bipin Savani
  • Sebastian Giebel
  • Emmanuelle Polge
  • Jordi Esteve
  • Arnon Nagler
  • Mohamad Mohty
Visa allt

Summary, in English

Patients with cytogenetically normal acute myeloid leukemia (CN-AML) can be subdivided by molecular mutations. However, data on the influence of combinations of different aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) is limited. Therefore, we performed a retrospective registry analysis on 702 adults with CN-AML 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. 2y-OS from HSCT was 81±5% in NPM1(mut)/FLT3(wt) (n=68), 75±3% in NPM1(wt)/FLT3(wt) (n=290), 66±3% in NPM1(mut)/FLT3-ITD (n=269) and 54±7% in NPM1(wt)/FLT3-ITD (n=75; p=0.003). Analysis of CEBPα among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBPα(mut) (n=13, 2y-OS:100%), and with a triple negative genotype (n=138, 2y-OS:77±3%). In a Cox-model of predefined factors, older age, presence of FLT3-ITD and >1 course of chemotherapy to reach CR were associated with inferior outcome. 2y-OS/LFS were 88±3%/79±4% in patients without any, 77±2%/73±3% with one, and 53±4%/50±4 with>=2 risk factors (p=0.002 for LFS, p=0.003 for OS). Hence, FLT3-ITD proofed to be the decisive molecular marker for outcome after HSCT for CN-AML in CR1, regardless of NPM1 mutational status, variations of transplant protocols, or development of GvHD. Age, FLT3-ITD and response to induction chemotherapy allow for a prognostic risk classification.

Publiceringsår

2015

Språk

Engelska

Sidor

2062-2069

Publikation/Tidskrift/Serie

Blood

Volym

126

Issue

17

Dokumenttyp

Artikel i tidskrift

Förlag

American Society of Hematology

Ämne

  • Hematology

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1528-0020