Diagnostic Accuracy and Prognostic Value of Flow Cytometry Versus PCR-Based Minimal Residual Disease Assessment in...

Measurable/minimal residual disease (MRD) is the most critical prognostic biomarker in leukemia. Multiparameter flow cytometry (MFC) and polymerase chain reaction (PCR)-based assays are the clinical standards for MRD detection; however, inter-method discordance complicates the clinical decision-making process. A systematic review and meta-analysis were conducted to evaluate the diagnostic accuracy of MFC compared to PCR and to delineate the prognostic significance of discordant MRD results. Following the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines, major databases were systematically searched for studies comparing MFC and PCR-based MRD assessments in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Diagnostic test accuracy was pooled using a bivariate random-effects model, and prognostic hazard ratios were synthesized using the restricted maximum likelihood models. Twenty-three non-randomized studies met the inclusion criteria of this review. In the diagnostic meta-analysis (12 studies), MFC demonstrated a pooled sensitivity of 76.2% (95% CI, 55.2-89.3) and a high pooled specificity of 96.0% (95% CI, 93.2-97.7) when compared with PCR, yielding an excellent area under the curve (AUC) of 0.965. Meta-regression identified leukemia subtype as a significant moderator (p=0.007), with MFC exhibiting lower diagnostic odds ratios in AML than in ALL. Survival analysis of MFC/PCR discordance (six studies) yielded a non-significant pooled HR of 1.27 (95% CI, 0.34-4.70) with extreme heterogeneity (I ²=89.2%), driven by the comparative baseline: isolated PCR positivity (MFC-/PCR+) conferred a significant survival advantage when compared to double-positive disease, but portended a significantly higher relapse risk when compared to double-negative disease. MFC is a highly specific and rapid modality for MRD detection, but it lacks the analytical sensitivity of PCR, particularly in AML. MFC/PCR discordance does not represent a uniform biological risk state; rather, its prognostic implications are highly context-dependent. The integration of both modalities provides a synergistic approach to optimize risk stratification and therapeutic tailoring in precision hematology.