Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis: Evolving Indications, Conditioning Strategies, and Outcomes.

Background/

Objectives

Myelofibrosis (MF) is a clonal myeloproliferative neoplasm driven by dysregulated JAK-STAT signaling, characterized by progressive marrow fibrosis, splenomegaly, constitutional symptoms, and increased risk of leukemic transformation. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative intervention. In Italy, allo-HCTs for myeloproliferative neoplasms (MPN, i.e., myelofibrosis, polycythaemia vera, and essential thrombocythaemia combined) increased by 163% from 2015 to 2025; MF-specific procedure counts were not separately available in this registry export, so this figure should not be read as MF-specific, with MPN accounting for 8% of all allogeneic procedures (n = 171) in 2025, showing a 29.5% year-on-year increase from 2024. Concurrently, the demographic profile shifted, with individuals aged 60 and over representing 38% of all recipients, surpassing other age groups for the first time in 2025.

Results

This review synthesizes current evidence on transplant indications and timing, pre-transplant management, donor selection, and conditioning regimen optimization, emphasizing the emerging role of treosulfan-based and dual-alkylator platforms, including the thiotepa-treosulfan-fludarabine (TTF) regimen. Post-transplant molecular MRD monitoring and relapse management are also discussed. Three-year overall survival in myelofibrosis ranges from about 59% to 67%, depending on donor type, with outcomes improving due to better patient selection, optimized conditioning, and supportive care.

Conclusions

Prospective randomized trials are urgently needed to validate optimal conditioning intensity, the role of novel JAK inhibitors in the peri-transplant period, and MRD-guided pre-emptive strategies.