Synergistic anti-tumor potential of epigenetic modulators and natural antioxidants in intensive care of hematological cancers: a schematic assessment of translational medicine and pathophysiological prospects
Abstract
Background: Hematologic malignancies such as acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and peripheral T-cell lymphoma (PTCL) remain difficult to treat. This systematic review and meta-analysis aimed to combine mechanistic, clinical, and pathophysiological knowledge to assist in guiding biomarkers to individualize therapy and ensure safety in the use of these regimens in hematologic cancer.
Methods: [PubMed], Scopus, Web of Science, and Google Scholar (2010-2025) were searched using PRISMA 2020 and included studies on human clinical research involving remission, progression-free survival, or overall survival. RoB 2 and ROBINS-I were used to determine risk of bias. The overall quality of evidence was assessed using GRADE. Meta-analysis was performed in RevMan 5.4.1 using a random-effects model to calculate pooled hazard ratios (HRs) and odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted according to intervention type and study design.
Results: Twelve studies were included. AML meta-analysis pooled OR 1.58 (95% CI 0.26-9.54), which was not significant (I2=91%). Analysis of the CLL pooled provided HR = 0.28 (95% CI 0.17-0.46), significant PFS benefit (I2=82%). MM meta-analysis generated HR = 0.67 (95% CI 0.53-0.84), which demonstrates the coherent survival benefit (I2 < 50%). Analysis of lymphoma studies pooled OR = 0.89 (95% CI 0.28-2.77), which was not significant (I2=90%), but sensitivity and subgroup analyses supported the robustness of findings. Risk of bias ranged from low to moderate, and overall evidence quality was moderate according to GRADE.
Conclusion: Venetoclax- and epigenetic-based combinations have a definite advantage in CLL and MM. AML and lymphoma outcomes are inconclusive because of significant heterogeneity. To increase combination strategies and clinical translation and guide critical-care supporting approaches, standardized endpoints, biomarker-driven stratification, and harmonized trial designs are required.
Abbreviations: AML: acute myeloid leukemia, CLL: chronic lymphocytic leukemia, MM: multiple myeloma, PTCL: peripheral T-cell lymphoma,
Keywords: Leukemia, Myeloid Acute; Leukemia, Lymphocytic, Chronic; B-Cell; Multiple Myeloma; Lymphoma, T-Cell.
Citation: Asghar N, Jahanzaib, Hussain A, Shaikh ARK, Kanwel S, Hussain Z, Khaliq H, Shah MA. Synergistic anti-tumor potential of epigenetic modulators and natural antioxidants in intensive care of hematological cancers: a schematic assessment of translational medicine and pathophysiological prospects. Anaesth. pain intensive care 2025;29(9):1302-12. DOI: 10.35975/apic.v29i9.3068
Received: August 20, 2025; Revised: August 26, 2025; Accepted: August 26, 2025
