Potential application ofIDH1andIDH2mutations as prognostic indicators in non-promyelocytic acute myeloid leukemia: a meta-analysis

Abstract

Recurrent mutations of isocitrate dehydrogenase isoforms 1 and 2 (IDH1 and IDH2) have recently been studied in adult patients with acute myeloid leukemia (AML). A meta-analysis was performed to demonstrate their controversial prognostic impacts. The associations of IDH1 or IDH2 mutations with other molecular abnormalities were also investigated. In patients with AML, IDH1/2 mutations were significantly associated with normal karyotype and isolated trisomy 8 (p < .05). After adjusting for well-studied prognostic factors, IDH1 mutation seems to be associated with subtle but significantly inferior event-free survival (EFS) (p = 0.02) and possible adverse overall survival (OS) (p = 0.13) in patients with AML, especially in the favorable genotype subset with mutated NPM1 but without FLT3-ITD mutation (p < 0.05). Longer OS (p = 0.01) and better EFS tendency (p = 0.18) are implicated in patients with IDH2 mutations, which suggests that IDH2 mutations appear to confer a favorable prognosis. Moreover, IDH1 and IDH2 mutations may play a more important role in abnormal cytogenetics subgroups such as isolated trisomy 8. Screening of IDH1/2 mutations could help to identify patients at high risk within some subsets of AML.

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

“…Besides, IDH mutations are particularly common in cytogenetically normal AML patients (CN-AML; ref. 9). For these reasons, prognostic availability of IDH mutations in IR-AML patients should be further explored.…”

Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China

“…Of note, gene mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) were reported recently not only in gliomas but also in AML (4,5). The prognostic significance of these mutations appears controversial in AML (6)(7)(8)(9)(10), although a metaanalysis suggests a poor outcome in cases with IDH1 mutations (11).…”

Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology

“…The recommendation for testing of other mutations in AML is supported by 21 studies, † † † † † comprising one SR based meta-analysis, 353 13 were deemed to have a low to moderate risk of bias, § § § § § and one was deemed to have a moderate risk of bias. 29 None of those studies were found to have methodological flaws that would raise concerns about the studies' findings.…”

“…Among studies of the effect of isocitrate dehydrogenase 1 (IDH1) mutation R132 in adult AML, one meta-analysis 353 found the mutation associated with a worse EFS, but not associated with OS. One NRCT 354 found the mutation to be associated with a worse OS and DFS, but that study combined the results of IDH1 and IDH2 mutations.…”

“…15 For mutations in IDH2 in adult AML, most studies combined the results of the R140 and R172 mutations, and some combined IDH2 results with those of IDH1. One meta-analysis 353 found improved OS, but no effect on EFS in AML with mutated IDH2. Two NRCTs 10,354 and 2 PCSs 351,352 found a worse prognosis with that mutation, although the worse prognosis was only associated with the R172 mutation in one study.…”