The Two-Step Allogeneic Stem Cell Transplant Is Associated with Excellent Engraftment, Improved Survival and Low Nonrelapse Mortality in Patients with Myelofibrosis

Myelofibrosis is a chronic myeloproliferative disorder primarily affecting older adults, and allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option. However, HSCT for myelofibrosis presents significant challenges, including high nonrelapse mortality (NRM) and an increased risk of graft failure. In this 20-year retrospective study, we evaluated outcomes for 32 myelofibrosis patients who underwent HSCT at our institution, with particular focus on a two-step transplant approach designed to optimize T-cell dosing by separating the lymphoid and myeloid graft components, with cyclophosphamide administered after the lymphoid infusion and before infusion of CD34-selected stem cells. Eighteen patients underwent transplantation using the two-step approach and demonstrated favorable outcomes, with 1-year and 5-year overall survival (OS) rates of 83% and 68%, respectively. NRM was reduced, with rates of 17% at 1 year and 23% at 5 years. Engraftment was robust, with median neutrophil and platelet recovery at 12 and 19 days, respectively, and a low graft failure rate of 5.9% despite the predominant use of reduced-intensity conditioning and haploidentical donors, compared with 17.5% graft failure among patients receiving a traditional one-step transplant. Across the entire cohort, OS was 66% at 1 year and 54% at 5 years, respectively, with NRM rates of 34% and 42% at 5 years, respectively. The cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD was 17% each. These findings suggest that the two-step transplant platform is a viable and effective strategy for improving HSCT outcomes in myelofibrosis, providing lower NRM and favorable engraftment profiles. Further studies are warranted to validate these results and refine HSCT protocols to reduce transplant-related mortality and improve long-term survival in patients with myelofibrosis.