Abstract Body

Current status of flow cytometry analysis of measurable residual disease in myelodysplastic neoplasms

AA van de Loosdrecht, LL Ngai, TM Westers, Cloos J.

Amsterdam University Medical Centers, location VU University MC, Cancer Center Amsterdam, The Netherlands

Accurate diagnosis in myelodysplastic neoplasms (MDS) necessitates additional sensitive and specific assays which can discriminate between MDS and non-MDS cytopenic patients, in those cases without molecular abnormalities, ring sideroblasts or other major morphologic dysplastic features in one or more lineages. The recent updated WHO classification (WHO2022) and ICC2022 on myeloid neoplasm contribute to a more refined classification of MDS and distinguish MDS from AML more accurately (Khoury JD et al. Leukemia 2022; Arber DA et al. Blood 2022). Due to the availability of huge data sets cytogenetic abnormalities as well as mutations are re-defined with diagnostic and prognostic implications that, in part, are translated into the risk models such as IPSS-Molecular (Bernard E et al. NeJMEvidence 2022). Since flow cytometry (FC) can identify aberrancies in myeloid progenitor cells and in maturing granulocytic, monocytic and erythroid lineages that are not recognised by cytology, FC may be instrumental in improving the diagnosis and classification of MDS (Van de Loosdrecht AA et al. Cytometry B Clin Cytom 2023; Wang W, Khoury JD Cytometry B Clin Cytom 2023). FC is even considered as co-criterion when regular diagnostic criteria are not met within the WHO/ICC2022 for CMML. In addition, FC aberrancies showed strong prognostic power beyond IPSS-Revised (Alhan C et al. Leukemia 2016; Oelschlaegel U et al. Cytometry B Clin Cytom 2023). Detecting measurable residual disease (MRD) in AML after second induction cycle of intensive chemotherapy has prognostic value and is currently implemented in the clinical decision for consolidation therapy (Jongen-Lavrencic M et al. N Engl J Med 2018; Lowenberg B et al. Blood Adv 2022). The ELN AML-MRD working party just updated the guidelines with novel experiences in the field of AML-MRD (Heuser M et al. Blood 2021). This is not yet established for MDS. However, increasing data support the role of MRD in MDS by tracking patient-specific mutations and using flow cytometry-definedleukemia-associated immunophenotypes (LAIP) where the LAIP is determined at diagnosis and followed during and after treatment (Ngai LL et al. [manuscript in prep]). In addition, a second method is based on the LAIP based different from normal (DfN) method where all LAIPs are evaluated at any measurement indicating possible clonal evolution. The detection of aberrant leukemic stem cells (IA-HSC) next to LAIP may further increase the accuracy of prognostication and hence clinical decision making in AML (Zeijlemaker W et al. Leukemia 2018; Ngai LL et al [submitted]). It is demonstrated that presence of IA-HSCs within MDS predicts leukemic progression indicating the clinical potential of IA-HSC as a prognostic biomarker (Van Spronsen M et al. Leukemia 2023 [epub ahead of print], Bachas C et al. Cytometry B Clin Cytom 2022). In addition, the presence of IA-HSCs correlated with perturbed hematopoiesis which is defined as disproportionally expanded CD34⁺ subsets. MRD assessments by the combination of molecular and FC-defined standardized platforms should be incorporated in emerging new clinical trials in MDS.