Rationale for JAK2 inhibition prior to HSCT in myelofibrosis. Splenomegaly contributing to hypersplenism-mediated sequestration of donor graft leading to primary graft failure, poor performance status and cachexia contributing to increased TRM, and hyper-inflammatory state contributing to increased risk of GVHD have all been identified as potential obstacles to successful outcome in HSCT of patients with MF. The use of a JAK2 inhibitor immediately prior to conditioning chemotherapy should result in reduction of splenomegaly, improvement in performance status, reversal of cachexia, suppression of circulating inflammatory cytokines. Therefore, the effects of JAK2 inhibition prior to HSCT is hypothesized to result in a decrease in rate of graft failure, TRM, and possibly GVHD.