Outcome of Acute Myeloid Leukemia Treatment and Isocitrate Dehydrogenase (IDH) Mutations: A Systematic Review and...

Background: Acute myeloid leukemia (AML) is a heterogeneous disease with diverse genetic alterations that influence prognosis and treatment outcomes. Isocitrate dehydrogenase (IDH) genes, particularly IDH1 and IDH2, have emerged as important prognostic biomarkers, but the impact of their mutations on survival remains controversial. This systematic review and meta-analysis aimed to evaluate the prognostic significance of IDH mutations in AML, focusing on overall survival (OS) and relapse-free survival (RFS). Materials and Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science to identify eligible studies published up to February 2025. Studies reporting associations between IDH mutations (IDH1 and IDH2) and survival outcomes in AML were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted or derived when necessary. Results: The analysis included 33 studies (n = 17,576). IDH2 mutations were associated with improved overall survival (HR = 0.70, 95% CI: 0.63-0.78) and relapse-free survival (HR = 0.65, 95% CI: 0.52-0.82), particularly in patients treated with IDH inhibitors. IDH1 mutations were associated with worse overall survival (HR = 1.16, 95% CI: 1.07-1.25) but showed no significant effect on relapse-free survival (HR = 1.03, 95% CI: 0.76-1.41). Subgroup analysis revealed a more favorable prognosis for IDH2 R140 mutations, whereas IDH2 R172 mutations showed heterogeneous outcomes across studies and treatment settings. Conclusion: IDH mutations have a heterogeneous prognostic impact in AML, with IDH2 mutations generally associated with better outcomes than IDH1 mutations. Larger, well-designed studies with comprehensive molecular profiling are needed to further clarify their prognostic implications.