Prognostic implications of the IDH1 synonymous SNP rs11554137 in pediatric/adult AML: a report from the Children's Oncology Group and SWOG.

Publication Type:

Journal Article

Source:

Blood, Volume 118, Issue 17, p.4561-6 (2011)

Keywords:

2011, Adolescent, Adult, Age of Onset, Center-Authored Paper, Child, Child, Preschool, Clinical Research Division, Clinical Trials as Topic, Female, Genomics Core Facility, Humans, Infant, Infant, Newborn, Leukemia, Myeloid, Acute, Male, Medical Oncology, Middle Aged, Mutation, Missense, Polymorphism, Single Nucleotide, Prognosis, Public Health Sciences Division, September 2011, Shared Resources, Societies, Medical, Young Adult

Abstract:

The IDH1 SNP rs11554137 was recently reported in association with poor prognosis in normal karyotype adult AML. We aimed to determine the prevalence, clinical associations, and prognostic significance of SNP rs11554137 in unselected pediatric and adult AML patients. Diagnostic marrow specimens from 527 AML patients treated on the pediatric trial COG-AAML03P1 (N=253) or adult SWOG trials (N=274) were analyzed for the presence of the IDH1 SNP. SNP rs11554137 was present in 11% of pediatric and adult AML patients. SNP status had no prognostic impact on survival in pediatric patients. In adult AML, overall survival (OS) from study entry for SNP-positive patients was 10% vs. 18% for SNP-negative patients (P=0.44). Among the 142 adult patients who achieved complete remission (CR), 5 year relapse-free survival (RFS) was significantly worse for SNP-positive patients (0% vs. 25%, P=0.0014). However, among adult patients with normal cytogenetics, FLT3/ITD was present in 90% of SNP-positive patients vs. 59% of SNP-negative patients (P=0.0053). Thus in multivariate analysis, adjusting for the effects of age, cytogenetics, and FLT3/ITD, the independent prognostic effect of SNP positivity was not statistically significant (HR=1.72, P=0.18). The clinical profile of SNP-positive patients suggests that SNP rs11554137 may have biologic effects which bear further investigation. The clinical trials in this study are registered at http://www.clinicaltrials.gov under NCT000707174 and NCT00899171.