JAK-2 inhibitors and allogeneic transplant in myelofibrosis

The activation of the JAK1/JAK2 pathway plays a crucial role in the pathogenesis of myelofibrosis. Treatment with the JAK2 inhibitor ruxolitinib demonstrated to reduce splenomegaly and symptoms in patients affected by myelofibrosis, leading to a significant improvement of overall survival in comparison with the supportive therapies. Taking in account this recent therapeutic progress, it is necessary to redefine the role of the allogeneic hematopoietic stem cell transplantation, which has been considered the only curative option for fit myelofibrosis patients up to now. In the era of JAK2 inhibitors, allogeneic transplant is still indicated in patients with intermediate-2 and high-risk myelofibrosis or red blood cell transfusion dependent patients or patients with unfavourable karyotype. There is no direct evidence to recommend which conditioning regimen should be preferentially adopted. Graft failure, relapse and transplant related mortality are still current issues of the allogeneic stem cell transplantation, particularly from unrelated donors. Ruxolitinib can be efficaciously included in the platform of allogeneic transplant. In fact, ruxolitinib treatment for 3-4 months before transplant has demonstrated to reduce spleen and improve performance status in about 30-50% of patients, without impairing the outcome of the subsequent transplant. Ruxolitinib has to stopped the day before conditioning to avoid rebound phenomenon. There are no sufficient data to recommend ruxolitinib administration after transplant with the aim of eradicating minimal residual disease and preventing relapse.