Authors (including presenting author) :
Lam WK(1), Wong TF(1), Lai LMC(1), Law WYF(1), Wong KKW(2), Sin YT(2), Li KS(2), Ha CY(2), Yip SF(1)
Affiliation :
(1)Department of Clinical Pathology, Tuen Mun Hospital, (2)Department of Medicine and Geriatrics, Tuen Mun Hospital
Introduction :
Measurable residual disease (MRD) monitoring is crucial for AML management. While molecular methods are valuable, they are limited to ~35% of patients. Multiparametric flow cytometry MRD (MFC-MRD) offers a broader approach. This pilot study evaluated a clinically validated MFC-MRD panel in adult AML.
Objectives :
1. Develop a local MFC-MRD assay.
2. Compare MFC-MRD applicability with molecular methods.
3. Assess MFC-MRD’s potential impact on management according to European LeukemiaNet (ELN) recommendations.
Methodology :
This prospective study enrolled adults (≥18 years) receiving intensive chemotherapy for AML from 1st June 2023 to 30th August 2024. Bone marrow aspirates at diagnosis and follow-up were analysed using the ELN MFC-MRD panel (up to cycle 3; positivity defined as ≥0.1%). Clinical team was blinded to the MFC-MRD results. Patient risk stratification (2022 ELN), treatment response and clinical progress were correlated with MFC-MRD.
Result & Outcome :
Results: Seventeen patients (median age 58; male:female 1.4:1) were enrolled (ELN risk stratification: favourable (17.6%, n=3), intermediate (41.2%, n=7), adverse (41.2%, n=7)). 26/27 (96.3%) post-treatment specimens yielded conclusive MFC-MRD results (all 17 patients had ≥1 conclusive result). MFC-MRD negativity rates: favourable-risk (100%), intermediate-risk (42.9%), adverse-risk (28.6%). MFC-MRD was applicable in all patients (100%) versus only 17.6% (n=3) with suitable molecular markers available (p< 0.001). MFC-MRD generally aligned with standard morphological and molecular MRD assessments.
Failing to achieve MFC-MRD negativity by cycle 3 (9/17, 52.9%) showed a tendency toward higher ELN risk, relapse/refractory disease, and poorer outcomes. Three had refractory disease (two died, median survival 7.2 months), one relapsed (4.4 months post-remission), and five underwent/planned allogeneic haematopoietic stem cell transplantation (allo-HSCT).
Of eight patients achieving MFC-MRD negativity, three (37.5%) were intermediate-risk. None of these three patients relapsed (follow-up 4.9-14.7 months), though two underwent/planned upfront allo-HSCT. MFC-MRD negativity in intermediate-risk patients might avoid upfront allo-HSCT according to ELN recommendations, potentially reducing costs and transplant-related morbidity/mortality.
Conclusion: This pilot evaluation of MFC-MRD in adult AML demonstrated broader applicability exceeding molecular methods. MFC-MRD positivity predicted relapse risk, while negativity may obviate upfront allo-HSCT in intermediate-risk patients. MFC-MRD is promising for refining AML management, and clinical implementation is ongoing.