Minimal residual disease assessment in hematologic malignancies: A systematic review highlighting global disparities and limited evidence from low- and middle-income countries

Abstract Background: Minimal residual disease (MRD) is an extremely important prognostic factor in hematological malignancies, with numerous studies in high-income countries (HICs) having confirmed its association with relapse and survival. Notwithstanding this, there is a paucity of data from low- and middle-income countries (LMICs), excluding universal access to evidence-based implementation of MRD-based treatment strategies. Objectives: This systematic review aimed to summarize the current evidence on MRD assessment in hematologic malignancies, with special reference to studies from LMICs. We assessed methods, time points, thresholds, prognostic value, and feasibility constraints for use in low-resource settings. Methods: We systematically reviewed studies from 2020 to 2025 that reported MRD results in hematologic malignancies. The studies were grouped by region (HIC vs. LMIC), MRD technology (flow cytometry, Polymerase Chain Reaction, Next-Generation Sequencing, Droplet Digital Polymerase Chain Reaction), time points of measurement, and survival or relapse outcomes reported. Results: A meta-analysis from Short et al. (2020) encompassing more than 11,000 patients mainly from HICs clearly showed that MRD negativity is strongly linked with better overall survival (HR ≈ 0.36) and relapse-free survival (HR ≈ 0.37). However, only ~5% of patients represented LMICs in this study. On the other hand, LMIC-specific evidence is still confined to small cohort studies. Patkar et al. (2023) from India (n=57) and certain Chinese studies (n=100–646) also indicated comparable correlations between MRD positivity and increased risk of relapse. MRD methods varied widely, with thresholds ranging from 0.001% to detectable presence. Implementation was often restricted to tertiary centers with advanced diagnostic capacity, limiting scalability across LMICs. Conclusions: Although MRD has shown prognostic relevance worldwide, the disparity in the availability and use of MRD testing within LMICs is high. The majority of existing evidence comes from HICs, with sparse but increasing data from upper-middle-income countries such as China and India. Standardized, resource-adjusted MRD protocols and further research within LMIC settings are necessary to facilitate equal access to MRD-guided therapies across the globe.