Comprehensive Characterization of Overt Myelofibrosis in an Asian Cohort: Phenotype, Mutation Landscape and...

Various prognostic scoring systems in myelofibrosis (MF) have been developed to guide clinical decision-making in MF. However, discrepancies between different scoring systems for individual patients remain poorly understood, which can result in conflicting treatment recommendations. Moreover, data regarding there applicability in Asian populations remain scarce. We conducted a retrospective analysis of patients with overt MF at National Taiwan University Hospital from November 1, 2006, to November 30, 2023. This study evaluates the distribution, concordance, and prognostic value of various scoring systems (IPSS, DIPSS, DIPSS+, MYSEC-PM, MIPSS70, MIPSS70+v2, GIPSS), focusing on the mutational landscape, particularly TP53 mutations, and cytopenic phenotypes in an Asian MF cohort. All prognostic systems effectively stratified patients by risk (p < 0.005); however, concordance between systems was low (Cohen's κ < 0.4, except for IPSS vs. DIPSS+). GIPSS demonstrated superior performance with a comparable C-index but lower Akaike and Bayesian information criterion values. Besides high-molecular risk mutations, TP53 mutations (5.2%) were associated with worse overall survival (OS) (5-year: 30% vs. 68%, p < 0.001) and a trend toward higher leukemic transformation (5-year: 22% vs. 10%, p = 0.055). Cytopenic phenotype (59%) was associated with a higher incidence of ASXL1 mutations (44% vs. 28%, p = 0.04). In multivariable analysis, elderly patients, higher-risk GIPSS, TP53 mutation and cytopenic phenotype were associated with a poorer OS. This study validated multiple prognostic scoring systems in an Asian MF cohort, with GIPSS showing superior risk stratification. Further, cytopenic phenotype and TP53 mutations were identified as independent factors linked to poorer survival.