Introduction
Philadelphia-negative myeloproliferative neoplasms (MPNs) represent a group of clonal hematopoietic stem cell disorders, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. These conditions can progress to blast phase (MPN-BP), a biologically distinct and highly aggressive entity characterized by the presence of ≥20% blasts in the blood or bone marrow. Historically, MPN-BP has been associated with dismal outcomes, with median survival typically under six months. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative approach, yet challenges such as relapse and non-relapse mortality persist.
Study Design
The study by Barbullushi et al. retrospectively analyzed outcomes in 51 consecutive adults undergoing 53 allo-HSCTs for MPN-BP at a single institution. The median age was 62 years, and most cases evolved from myelofibrosis. JAK2 was the predominant driver mutation. The primary endpoints included overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). Secondary endpoints focused on engraftment kinetics and graft-versus-host disease (GVHD).
Key Findings
Survival Outcomes
Neutrophil engraftment occurred in all but two patients (median 12 days). At 1-year follow-up, cumulative incidences were 35.8% for grade II-IV acute GVHD and 7.5% for moderate-severe chronic GVHD. Relapse and non-relapse mortality rates were 44.3% and 25.8%, respectively. The 1-year OS and DFS were 43.4% and 37.7%, with relapse being the leading cause of death.
Genetic and Clinical Predictors
Multivariable analysis identified TP53 mutations and higher peripheral blast burden as significant adverse predictors of OS. Conversely, CALR mutations appeared to be associated with improved OS. Peripheral blast count also independently predicted relapse, emphasizing its utility in pre-transplant risk stratification.
Expert Commentary
The study underscores the curative potential of allo-HSCT for MPN-BP, with approximately one-third of patients achieving long-term survival. These findings align with prior literature highlighting the importance of early referral for transplant evaluation. However, the high relapse rate remains a critical challenge, necessitating novel strategies such as targeted conditioning regimens or post-transplant maintenance therapy. The association of TP53 mutations with poor outcomes echoes similar observations in other hematologic malignancies, reinforcing the need for mutation-specific therapeutic approaches.
Conclusion
This study provides valuable insights into the role of allo-HSCT in MPN-BP, demonstrating a cure rate of approximately one-third. Peripheral blast count and TP53 mutation status emerge as actionable biomarkers for refining transplant candidacy and prognostic stratification. Future research should focus on optimizing conditioning regimens and exploring adjunctive therapies to mitigate relapse risk.
References
Barbullushi K, et al. Outcomes of allogeneic transplantation in blast-phase myeloproliferative neoplasms: one-third achieve long-term survival. Bone Marrow Transplant. 2026.
