Measurable Residual Disease Monitoring by Multiparameter Flow Cytometry and Relapse Prediction in Adult Acute Myeloid Leukemia

Abstract

Roughly half the adults who achieve complete remission from acute myeloid leukaemia go on to relapse, and morphological remission cannot distinguish them in advance. Flow cytometric residual disease can, but the threshold that defines a positive result was set by consensus rather than derived from data, and the largest analysis to test it found it wanting. Objectives: To review the published evidence on measurable residual disease assessed by multiparameter flow cytometry in adult acute myeloid leukaemia: what
it predicts, when it should be measured, how the 0.1 per cent threshold performs, and what a positive or negative result should change. Material and Methods: Narrative review of cooperative group trials, consensus documents, methodological analyses and surveillance cohorts indexed in PubMed and the major haematology journals. Studies were eligible if they reported the prognostic value of flow cytometric residual disease in a defined adult acute myeloid leukaemia population, compared timepoints or thresholds, or examined assay performance. No new patient data were generated and no patients were recruited; every estimate quoted is one published by the original investigators. Results: The European LeukemiaNet defines positivity at 0.1 per cent of CD45-expressing cells carrying the target immunophenotype. Applied to 2,051 patients across four cooperative group cohorts in which residual disease did not guide treatment, dichotomising at that value produced suboptimal relapse-risk stratification, and levels below it remained prognostically informative. In a surveillance cohort of 136 samples preceding relapse by a median of 2.45 months and
155 taken during sustained remission, a threshold of 0.040 per cent gave sensitivity of 74 per cent and specificity of 87 per cent, against 51 and 98 per cent at 0.1 per cent. Assessment after two consolidation cycles outperformed assessment after induction, with hazard ratios of 3.635 for relapse-free and 3.511 for overall survival. Among 273 patients assessed at both cycles, 91.8 per cent of those negative after cycle 1 remained negative, while only 53.2 per cent of those positive remained positive. Conclusion: A negative result is stable and reliable; a positive result at one timepoint is frequently not confirmed at the next. The 0.1 per cent threshold buys
specificity at a cost of missing roughly half of impending relapses, which is defensible only if the intended action carries substantial risk. Abbreviations: AML – Acute Myeloid Leukaemia, MRD – Measurable Residual Disease, MFC – Multiparameter Flow Cytometry, LAIP – Leukaemia-Associated Immunophenotype, DfN – Different-from-Normal, ELN – European LeukemiaNet, CR – Complete Remission, RFS – Relapse-Free Survival, OS – Overall Survival, alloHCT – Allogeneic Haematopoietic Cell Transplantation, LSC – Leukaemic Stem Cell, WBC – White Blood Cells.