Sequential High-Dose Ruxolitinib and Low-Dose Splenic Irradiation for Pretransplant Management of Splenomegaly Before Allogeneic Hematopoietic Cell Transplantation With Fludarabine/Busulfan-Based Conditioning in Myelofibrosis.

Abstract

Background: Significant splenomegaly remains a major barrier to successful allogeneic hematopoietic cell transplantation (allo-HCT) in myelofibrosis (MF), contributing to delayed engraftment and an increased risk of graft failure. Systemic JAK inhibition and splenic irradiation are commonly used as independent pretransplant strategies; however, evidence regarding their sequential use and integration into contemporary conditioning platforms remains limited.

Methods: We conducted a single-center retrospective study of nine patients with MF who underwent allo-HCT between 2020 and 2025. Patients received sequential high-dose ruxolitinib followed by low-dose splenic irradiation (LDSI) as pretransplant spleen-directed therapy prior to a fludarabine/busulfan-based conditioning regimen. Spleen response, engraftment kinetics, and transplant outcomes were evaluated.

Results: High-dose ruxolitinib reduced median spleen length from 185 to 172 mm, followed by a further decrease to 137 mm after LDSI. All patients achieved engraftment, with median times to neutrophil and platelet recovery of 15 and 19 days, respectively. The cumulative incidence of any-grade acute graft-versus-host disease (GVHD) was 22.2%, and moderate chronic GVHD occurred in 11.1%. The estimated 2-year overall survival was 88.9%, and the estimated 2-year GVHD-free and relapse-free survival (GRFS) was 76.2%. The estimated 2-year cumulative incidence of relapse was 12.7%, and estimated non-relapse mortality was 11.1%.

Conclusion: Sequential high-dose ruxolitinib followed by LDSI appeared feasible and was associated with stepwise pretransplant spleen reduction and encouraging early transplant outcomes following allogeneic HCT with fludarabine/busulfan-based conditioning. Given the small sample size and absence of a comparator group, this combined systemic and local spleen-directed strategy warrants further evaluation in prospective multicenter studies.

Trial registration: The authors have confirmed clinical trial registration is not needed for this submission.