A novel approach to defining progression in MDS and precursor myeloid conditions in The MDS Natural History Study

Patients at risk for progression from myeloid precursor states (ICUS, CCUS) to MDS are not well defined. Epidemiologic risk factors, clonal changes for MDS development, and evolution from one MDS state to another (lower- (LR) or higher-risk (HR) disease or leukemia [AML]) are available in the MDS NHS, a prospective cohort enrolled at diverse US sites. Extensive clinical data and biospecimens are collected at baseline and follow-up. A total of 1,177(56%) individuals with MDS or MDS-related precursor conditions (ICUS/IDUS, CCUS, and MDS/MPN overlap) were enrolled and diagnosed in the MDS NHS. The median age was 74 years with 89% 60 years of age or older and a majority were male. Median follow-up time was 1.6 years and was similar among ICUS/IDUS, CCUS and MDS. During follow-up period, 68% of participants terminated the study, 35% died, and 38% had disease progression. Using a refined clinical definition of progression, the greatest proportion progression was observed among HR-MDS (116, 73%), followed by LR-MDS (170, 52%); fewer progression events were observed among CCUS (65, 22%) and ICUS/IDUS participants (46, 17%). Predictors of progression are delineated including female sex; higher quantity of mutations; the presence of TP53 mutation mutation: Any change or alteration in a gene. A mutation may cause disease or may be a normal variation. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a mutation in the PIG-A gene of a single stem cell in the bone marrow. and poor/very poor cytogenetic score. Based on this prospective data, guidelines for clinical management including monitoring and surveillance are outlined. The MDS NHS provides real-world data to illustrate how clinical and genotypic differences inform the classification, disease course, and approach to therapy with informed monitoring guidelines for patients. NCT02775383.