The role of JAK inhibitors in hematopoietic cell transplantation

Abstract

The Janus Kinase (JAK)/Signal Transducers and Activators of Transcription (STAT) pathway is essential for both the regulation of hematopoiesis and the control of inflammation. Disruption of this pathway can lead to inflammatory and malignant disease processes. JAK inhibitors, designed to control the downstream effects of pro-inflammatory and pro-angiogenic cytokines, have been successfully used in pre-clinical models and clinical studies of patients with autoimmune diseases, hematologic malignancies, and the hematopoietic cell transplantation (HCT) complication graft versus host disease (GVHD). In the last decade, JAK inhibitors Ruxolitinib, Fedratinib, and most recently Pacritinib have been United States Federal Drug Administration (FDA) approved for the treatment of myelofibrosis (MF). Ruxolitinib was also recently approved for the treatment of steroid refractory acute as well as chronic GVHD; JAK inhibitors are currently under evaluation in the pre-HCT setting in MF and for the prevention of GVHD. This review will focus on the role of JAK inhibitors in the treatment of hematologic malignancies, the potential function of pre-HCT JAK inhibitors in patients with MF, and the role of JAK inhibitors in the prevention and treatment of acute and chronic GVHD.