Efficacy and prognosis of hypomethylating agent therapy in patients with myelodysplastic syndromes with bone marrow fibrosis

Myelodysplastic syndromes with bone marrow fibrosis (MDS-F) have been delineated as a distinct disease subtype in the latest WHO classification; nevertheless, specific therapeutic strategies for this entity remain undefined. This study was conducted to systematically evaluate the impact of bone marrow fibrosis on treatment response, long-term survival, and adverse event profiles in patients with MDS-F undergoing Hypomethylating agents (HMA) therapy. This retrospective analysis included 200 patients with MDS with excess blasts (MDS-EB) who received HMA monotherapy at Shanghai Sixth People's Hospital between March 2010 and March 2023. Survival analyses were performed using the Kaplan–Meier method, and prognostic factors were evaluated with Cox proportional hazards regression models. The median age was 65 years; 118 patients had MDS‑EB‑1 and 82 had MDS‑EB‑2. Overall response rates (ORR) were comparable between MF‑2/3 and MF‑0/1 groups (50.9% vs. 53.7%, P = 0.873), as were complete remission (CR) rates (26.4% vs. 25.2%, P = 1.000). However, patients with MF‑2/3 had a significantly shorter median overall survival (14 vs. 18 months, P = 0.020) and a markedly shorter median duration of response (5 vs. 9 months, P = 0.036). Multivariate analysis confirmed MF‑2/3 as an independent adverse prognostic factor (HR = 1.449, 95% CI 1.022–2.055, P = 0.037). The incidence of grade 4 neutropenia (88.7% vs. 74.8%, P = 0.035) and grade 4 infections (66.0% vs. 44.9%, P = 0.008) was significantly higher in the MF‑2/3 group, along with treatment delays (32.1% vs. 6.8%, P < 0.001) and HMA‑related mortality (26.4% vs. 7.5%, P = 0.001). In a subset of 82 patients with NGS data, TP53 mutations were enriched in the MF‑2/3 group (30.4% vs. 10.1%, P = 0.055). Post‑treatment biopsies showed fibrosis regression in 12.0% and progression in 12.6%, with no significant association between dynamic fibrosis changes and survival. Patients with MDS-F achieve short-term responses to HMA therapy comparable to those of patients with MF-0/1. Nonetheless, MF-2/3 portends inferior long-term survival and a substantially elevated risk of severe infectious complications, representing an independent adverse prognostic determinant.