IPSS-M Predicts Survival Outcomes Significantly Better Than IPSS-R in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for Myelodysplastic Neoplasms

Abstract

Background The newly published molecular International Prognostic Scoring System (IPSS-M) represents a powerful risk stratification tool for treatment decision-making in myelodysplastic neoplasms (MDS); however, its utility in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains to be fully explored. Methods We retrospectively analyzed a large multicenter cohort of 347 MDS patients who underwent allo-HSCT between January 2017 and October 2022. The prediction accuracy of IPSS-M at diagnosis for 3-year survival outcomes was assessed and compared to that of the conventional revised International Prognostic Scoring System (IPSS-R). Results Among the 347 patients, median age at transplant was 48.3 years and 41.2% of patients were female. According to IPSS-M, patients were clustered as very low risk (1.2%), low risk (11.2%), moderately low risk (11.5%), moderately high risk (18.2%), high risk (33.4%), and very high risk (24.5%), resulting in a restratification of 49.3% of the entire cohort when compared with IPSS-R. Of these reclassified patients, 52.6% patients were upstaged and 47.4% were downstaged. Median follow-up time among the survivors was 28.6 (range, 4.7 to 76.6) months. With the IPSS-M model, overall survival (OS) and leukemia-free survival (LFS) discrimination was refined relative to the IPSS-R as evidenced by a 7.0 percentage- and 5.7 percentage-point increase in the concordance index (C-index), which was further supported by the lower Akaike Information Criterion and higher C-indexes in multivariate analyses. Among patients undergoing haploidentical HSCT, IPSS-M model also demonstrated significantly improved prognostic performance for LFS versus IPSS-R (C-index, 0.707 vs 0.604) which was validated by multivariate analyses. When restricting our analyses to younger patients (<49 years) and patients carrying detectable mutations, IPSS-M retained greater prognostic value with respect to OS and LFS; while it failed to stratify individual probability of OS and LFS in their counterparts. Conclusions IPSS-M was confirmed to increase prognostic discrimination at the individual level and is applicable to transplant-specific settings, which also had an advantage for subjects carrying mutations and younger patients.