Outcome of Acute Myeloid Leukemia Treatment and IDH Mutations: A Systematic Review and Meta-Analysis Study

Fereshteh  Ameli; Alireza  Abdollahi; Samaneh  Salarvand; Dorsa  Ghasemi

doi:10.18502/ijhoscr.v20i2.21782

Fereshteh Ameli Department of Pathology, School of Medicine, Tehran University of Medical Science, Iran
Alireza Abdollahi Department of Pathology, School of Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences
Samaneh Salarvand Department of Pathology, School of Medicine, Vali Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences
Dorsa Ghasemi Department of Pathology, School of Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences

DOI: https://doi.org/10.18502/ijhoscr.v20i2.21782

Keywords: Acute myeloid leukemia; IDH mutations; Prognosis; Survival

Abstract

Background: Acute myeloid leukemia (AML) is a heterogeneous disease with diverse genetic alterations influencing prognosis and treatment outcomes. Isocitrate dehydrogenase (IDH) genes, particularly IDH1 and IDH2, have emerged as important biomarkers, but the prognostic impact of their mutations 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 the association 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 linked to poor outcomes (OS HR = 1.16, 95% CI: 1.07–1.25; RFS HR = 1.03, 95% CI: 0.76–1.41). Subgroup analysis showed a more favorable prognosis for IDH2 R140 mutations, whereas IDH2 R172 mutations demonstrated heterogeneous outcomes across studies and treatment settings.

Conclusion: IDH mutations have a significant but heterogeneous prognostic impact in AML, with IDH2 mutations generally associated with better outcomes compared to IDH1 mutations. Larger, well-designed studies with comprehensive molecular profiling are needed to clarify the prognostic implications of IDH mutations in AML.