Integrative prognostic risk score in acute myeloid leukemia with normal karyotype.
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Integrative prognostic risk score in acute myeloid leukemia with normal karyotype. / Damm, Frederik; Heuser, Michael; Morgan, Michael; Wagner, Katharina; Görlich, Kerstin; Grosshennig, Anika; Hamwi, Iyas; Thol, Felicitas; Surdziel, Ewa; Fiedler, Walter; Lübbert, Michael; Kanz, Lothar; Reuter, Christoph; Heil, Gerhard; Delwel, Ruud; Löwenberg, Bob; Valk, Peter J M; Krauter, Jürgen; Ganser, Arnold.
In: BLOOD, Vol. 117, No. 17, 17, 2011, p. 4561-4568.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Integrative prognostic risk score in acute myeloid leukemia with normal karyotype.
AU - Damm, Frederik
AU - Heuser, Michael
AU - Morgan, Michael
AU - Wagner, Katharina
AU - Görlich, Kerstin
AU - Grosshennig, Anika
AU - Hamwi, Iyas
AU - Thol, Felicitas
AU - Surdziel, Ewa
AU - Fiedler, Walter
AU - Lübbert, Michael
AU - Kanz, Lothar
AU - Reuter, Christoph
AU - Heil, Gerhard
AU - Delwel, Ruud
AU - Löwenberg, Bob
AU - Valk, Peter J M
AU - Krauter, Jürgen
AU - Ganser, Arnold
PY - 2011
Y1 - 2011
N2 - To integrate available clinical and molecular information for cytogenetically normal acute myeloid leukemia (CN-AML) patients into one risk score, 275 CN-AML patients from multicenter treatment trials AML SHG Hannover 0199 and 0295 and 131 patients from HOVON/SAKK protocols as external controls were evaluated for mutations/polymorphisms in NPM1, FLT3, CEBPA, MLL, NRAS, IDH1/2, and WT1. Transcript levels were quantified for BAALC, ERG, EVI1, ID1, MN1, PRAME, and WT1. Integrative prognostic risk score (IPRS) was modeled in 181 patients based on age, white blood cell count, mutation status of NPM1, FLT3-ITD, CEBPA, single nucleotide polymorphism rs16754, and expression levels of BAALC, ERG, MN1, and WT1 to represent low, intermediate, and high risk of death. Complete remission (P = .005), relapse-free survival (RFS, P < .001), and overall survival (OS, P < .001) were significantly different for the 3 risk groups. In 2 independent validation cohorts of 94 and 131 patients, the IPRS predicted different OS (P < .001) and RFS (P < .001). High-risk patients with related donors had longer OS (P = .016) and RFS (P = .026) compared with patients without related donors. In contrast, intermediate-risk group patients with related donors had shorter OS (P = .003) and RFS (P = .05). Donor availability had no impact on outcome of patients in the low-risk group. Thus, the IPRS may improve consolidation treatment stratification in CN-AML patients. Study registered at www.clinicaltrials.gov as #NCT00209833.
AB - To integrate available clinical and molecular information for cytogenetically normal acute myeloid leukemia (CN-AML) patients into one risk score, 275 CN-AML patients from multicenter treatment trials AML SHG Hannover 0199 and 0295 and 131 patients from HOVON/SAKK protocols as external controls were evaluated for mutations/polymorphisms in NPM1, FLT3, CEBPA, MLL, NRAS, IDH1/2, and WT1. Transcript levels were quantified for BAALC, ERG, EVI1, ID1, MN1, PRAME, and WT1. Integrative prognostic risk score (IPRS) was modeled in 181 patients based on age, white blood cell count, mutation status of NPM1, FLT3-ITD, CEBPA, single nucleotide polymorphism rs16754, and expression levels of BAALC, ERG, MN1, and WT1 to represent low, intermediate, and high risk of death. Complete remission (P = .005), relapse-free survival (RFS, P < .001), and overall survival (OS, P < .001) were significantly different for the 3 risk groups. In 2 independent validation cohorts of 94 and 131 patients, the IPRS predicted different OS (P < .001) and RFS (P < .001). High-risk patients with related donors had longer OS (P = .016) and RFS (P = .026) compared with patients without related donors. In contrast, intermediate-risk group patients with related donors had shorter OS (P = .003) and RFS (P = .05). Donor availability had no impact on outcome of patients in the low-risk group. Thus, the IPRS may improve consolidation treatment stratification in CN-AML patients. Study registered at www.clinicaltrials.gov as #NCT00209833.
KW - Adult
KW - Humans
KW - Middle Aged
KW - Risk Factors
KW - Adolescent
KW - Young Adult
KW - Predictive Value of Tests
KW - Prognosis
KW - Proportional Hazards Models
KW - Hematopoietic Stem Cell Transplantation
KW - Transplantation, Homologous
KW - Karyotyping
KW - Tumor Markers, Biological/genetics
KW - Clinical Trials as Topic/statistics & numerical data
KW - Leukemia, Myeloid, Acute/genetics/mortality/therapy
KW - Multicenter Studies as Topic/statistics & numerical data
KW - Adult
KW - Humans
KW - Middle Aged
KW - Risk Factors
KW - Adolescent
KW - Young Adult
KW - Predictive Value of Tests
KW - Prognosis
KW - Proportional Hazards Models
KW - Hematopoietic Stem Cell Transplantation
KW - Transplantation, Homologous
KW - Karyotyping
KW - Tumor Markers, Biological/genetics
KW - Clinical Trials as Topic/statistics & numerical data
KW - Leukemia, Myeloid, Acute/genetics/mortality/therapy
KW - Multicenter Studies as Topic/statistics & numerical data
M3 - SCORING: Journal article
VL - 117
SP - 4561
EP - 4568
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 17
M1 - 17
ER -
