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

Schmid, Christoph ; Labopin, Myriam ; Socié, Gerard ; Daguindau, Etienne ; Volin, Liisa ; Huynh, Anne ; Bourhis, Jean Henri ; Milpied, Noel ; Cornelissen, Jan and Chevallier, Patrice , et al. (2015) In Blood 126(17). p.2062-2069
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
126
issue
17
pages
2062 - 2069
publisher
American Society of Hematology
external identifiers
  • pmid:26351297
  • wos:000366389200018
  • scopus:84944931277
  • pmid:26351297
ISSN
1528-0020
DOI
10.1182/blood-2015-06-651562
language
English
LU publication?
yes
id
52d8bed0-a9a2-4d59-bdbf-64b4a7718625 (old id 8042796)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26351297?dopt=Abstract
date added to LUP
2016-04-01 09:48:51
date last changed
2024-10-06 13:23:36
@article{52d8bed0-a9a2-4d59-bdbf-64b4a7718625,
  abstract     = {{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.}},
  author       = {{Schmid, Christoph and Labopin, Myriam and Socié, Gerard and Daguindau, Etienne and Volin, Liisa and Huynh, Anne and Bourhis, Jean Henri and Milpied, Noel and Cornelissen, Jan and Chevallier, Patrice and Maertens, Johan and Jindra, Pavel and Blaise, Didier and Lenhoff, Stig and Ifrah, Norbert and Baron, Frédéric and Ciceri, Fabio and Gorin, Claude and Savani, Bipin and Giebel, Sebastian and Polge, Emmanuelle and Esteve, Jordi and Nagler, Arnon and Mohty, Mohamad}},
  issn         = {{1528-0020}},
  language     = {{eng}},
  number       = {{17}},
  pages        = {{2062--2069}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Outcome and risk factor analysis of molecular subgroups in cytogenetically normal AML treated by allogeneic transplantation.}},
  url          = {{http://dx.doi.org/10.1182/blood-2015-06-651562}},
  doi          = {{10.1182/blood-2015-06-651562}},
  volume       = {{126}},
  year         = {{2015}},
}