Correlation Between Isocitrate Dehydrogenase Gene Aberrations and Prognosis of Patients with Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis.

Abstract

<b>Purpose:</b> Whether isocitrate dehydrogenase (<i>IDH</i>) gene aberrations affected prognosis of patients with acute myeloid leukemia (AML) was controversial. Here, we conducted a meta-analysis to evaluate their prognostic value.<b>Experimental Design:</b> PubMed, Embase, Cochrane, and Chinese databases were searched to identify studies exploring how <i>IDH</i> gene aberrations affected AML outcome. Pooled HRs and relative risks (RR) were calculated, along with 95% confidence intervals (CI).<b>Results:</b> Thirty-three reports were included. <i>IDH</i> mutations seemed not to affect overall survival (OS: HR, 1.05; 95% CI, 0.89-1.23) and event-free survival (EFS: HR, 0.97; 95% CI, 0.80-1.18) when considered as a single factor, but improved accumulative incidence of relapse (CIR: HR, 1.44; 95% CI, 1.18-1.76) in patients with intermediate-risk karyotypes (IR-AML). However, <i>IDH1</i> mutation conferred worse OS (HR, 1.17; 95% CI, 1.05-1.31) and EFS (HR, 1.29; 95% CI, 1.07-1.56), especially in patients with normal cytogenetics (OS: HR, 1.21; 95% CI, 1.01-1.46; EFS: HR, 1.56; 95% CI, 1.23-1.98). Prognosis of the <i>IDH1</i> single-nucleotide polymorphism rs11554137 was also poor (OS: HR, 1.34; 95% CI, 1.03-1.75). <i>IDH2</i> mutation improved OS (HR, 0.78; 95% CI, 0.66-0.93), particularly in IR-AML patients (OS: HR, 0.65; 95% CI, 0.49-0.86). The <i>IDH2 (R140)</i> mutation was associated with better OS among younger cases (HR, 0.64; 95% CI, 0.49-0.82). Treatment outcome was poor [RR for complete remission rates in <i>IDH1</i> mutation: 1.21; 95% CI, 1.02-1.44; <i>IDH2</i> (<i>R172</i>) mutation: 2.14; 95% CI, 1.61-2.85].<b>Conclusions:</b> Various subtypes of <i>IDH</i> mutations might contribute to different prognosis and be allowed to stratify IR-AML further. <i>Clin Cancer Res; 23(15); 4511-22. ©2017 AACR</i>.