Allogeneic transplantation for myelofibrosis: for whom, when, and what are the true benefits?

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative therapy for myelofibrosis. Despite improved outcomes, morbidity and mortality of HSCT remain high. Here we examine recent data on patient selection, timing, and outcomes of HSCT in myelofibrosis.

While there is a general effort to restrict HSCT to transplant-eligible intermediate-2 and high-risk patients, this group has comparatively worse HSCT outcomes, largely driven by their high transplant-related mortality (TRM). When adjusted for age, reduced intensity conditioning (RIC) has shown superior outcomes compared with myeloablative conditioning (MAC), making RIC-HSCT a viable option for older patients. Emerging concepts include the use of ruxolitinib pretransplant, optimizing MAC to decrease toxicity, and use of posttransplant JAK2-mutant allele burden to guide prophylactic immunotherapy to prevent relapse. The recognition of prognostic significance of somatic mutations in the ASXL1, EZH2, SRSF2, and IDH1/2 genes, and the improved assessment of risk of leukemic transformation have added a new dimension to risk stratification.

Improving our understanding of molecular genetics and leukemic transformation holds promise for more precise patient selection for HSCT. Although RIC-HSCT may reduce TRM, further studies are needed to optimize conditioning regimens and to define the optimal timing of HSCT.