Optimization of allogeneic hematopoietic cell transplantation for patients with myelofibrosis treated with ruxolitinib: eligibility, best practices, and improving transplant outcomes

Allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment for myelofibrosis (MF), and current guidelines recommend assessing all patients with MF for eligibility. Several patient- and disease-specific factors impact transplantation outcomes, and timely assessment of potential transplant candidates is key to optimizing post-HCT outcomes. The role of HCT in the treatment of MF continues to evolve, with the adoption of newer and safer approaches, enhanced donor availability, use of reduced-intensity conditioning, improvements in graft-versus-host disease (GVHD) prophylaxis and treatment, and greater understanding of high-risk clinical and molecular features of the disease. These developments highlight the importance of early and ongoing assessment throughout the MF disease course to optimize eligibility and consideration for HCT. Ruxolitinib is approved for first-line treatment of intermediate- or high-risk MF, and emerging data have clarified the important role of ruxolitinib in not only optimizing clinical status before HCT but also mitigating and treating post-HCT complications in patients with MF, notably acute and chronic GVHD and relapse. Here we review strategies for optimizing clinical outcomes in patients considered for and undergoing HCT for MF treated with ruxolitinib. We discuss strategies for appropriate patient and donor selection, optimization of ruxolitinib therapy in the pre- and peri-HCT periods, choice of conditioning regimen, GVHD prophylaxis, post-HCT management of GVHD, continued monitoring for MF relapse, and the role of post-HCT ruxolitinib maintenance to reduce risks of GVHD and disease relapse.