How we manage JAK inhibition in allogeneic transplantation for myelofibrosis

Hematopoietic stem cell transplantation (HCT) is currently the only curative treatment for myelofibrosis (MF), but this option is complicated by high incidences of associated morbidity and mortality. Ruxolitinib, a janus-activated kinase (JAK) 1/2 inhibitor, has proven to be beneficial in reduction of splenomegaly, improvement of constitutional symptoms, and possibly in overall survival. However, use of JAK inhibitors in the peritransplant period has been complicated by unpredictable response, return of MF symptoms or cytokine storm reaction upon discontinuation, and lack of long-term response data. This review considers the current limited available data on JAK inhibitor use prior to HCT, including common side effects and possible impact of severe adverse events on discontinuation of the drug. We provide our experience and recommendations regarding use of JAK inhibition in patients undergoing HCT. Additional studies are needed to determine the optimal schedule of JAK inhibitors in the transplant protocols and their impact on engraftment, graft-versus-host disease, and survival.