Variables associated with outcome in patients with Philadelphia chromosome-negative accelerated- or blast-phase myeloproliferative neoplasms

Background: Poor outcomes have been reported when patients with myeloproliferative neoplasm (MPN) progress to the accelerated phase (AP) or blast phase (BP). Methods: Data on consecutive patients with Ph − MPN-AP/BP diagnosed and treated at three hospitals between 1 January 2015 and 18 July 2025 were reviewed. Efficacy and a Cox regression risk model was used to identify clinical variables associated with the outcome. Results: Data on 88 consecutive patients with Ph− MPN-AP/BP (32 AP and 56 BP) were reviewed. The median follow-up was 16 months. In MPN-AP, treatment with hypomethylating agents (HMA) + ruxolitinib or HMA + venetoclax achieved comparable response rates (returning to CP, 63% vs. 75%, p = 0.551). In MPN-BP, treatment with HMA + venetoclax or intensive chemotherapy achieved comparable response rates. The median survival was significantly longer in patients with MPN-AP than in those with MPN-BP (32 months [95%CI 6–58 months] versus 12 months [95%CI 9–15 months, p = 0.039]). In patients with MPN-AP, older age was significantly associated with poorer survival. In patients with MPN-BP, multivariate analysis revealed that WBC count ≥ 55 × 109/L, prior myelofibrosis history, and adverse karyotype were significantly associated with poorer survival; whereas HMA + venetoclax or intensive chemotherapy were associated with longer survival. In the 70 AP or BP patients with next-generation sequencing data TP53 , EZH2 , and SF3B1 mutations were associated with poorer survival. Conclusion: TP53 , EZH2 , and SF3B1 mutations predicted poor survival except adverse clinical variables. HMA + venetoclax or intensive chemotherapy might benefit patients with MPN-BP.