Impact of High-Risk Mutations and Treatment Intensity in Accelerated-Phase Blast-Phase MPN Without Adverse-Risk Karyotype and TP53.

The prognostic significance of myelodysplasia-related gene mutations (MDS-RGMs), defined by the ELN 2022 classification and Mutation-Enhanced International Prognostic Score System high-risk mutations (MIPSS70-HRM), in accelerated-phase (AP) and blast-phase (BP) myeloproliferative neoplasms (MPNs) remains unclear. We conducted a retrospective study of 101 AP/BP MPN patients with intermediate-risk cytogenetics, excluding TP53 mutations and adverse-risk karyotypes. We evaluated whether MDS-RGM or MIPSS70-HRM predicted treatment response, overall survival (OS), or disease-free survival (DFS) and whether treatment intensity affected OS. Patients included AP (29.7%) and BP (70.3%), with 55% receiving intensive therapy. Allogeneic stem cell transplant (ASCT) significantly improved OS (HR 0.31, 95% CI 0.19-0.50; p < 0.0001), as did AP versus BP at transformation (HR: 0.43, 95% CI 0.26-0.73; p = 0.0016). Among patients ≤ 70 years with ECOG 0-1 (N = 77), ASCT and reversion to chronic-phase MPN (cMPN) were associated with longer OS (p < 0.0001 and p = 0.0475). Treatment intensity alone did not significantly affect OS (p = 0.1991).