Allogeneic stem cell transplant for myelofibrosis patients over age 60: likely impact of the JAK2 inhibitors.

Abstract

The myeloproliferative neoplasm, myelofibrosis (MF), has only one therapeutic intervention that is potentially curative in these individuals, specifically that of allogeneic stem cell transplantation (ASCT). ASCT has been utilized up to this juncture, primarily in younger individuals with higher risk disease. There is more limited data on outcomes in individuals over the age of 60 years. The choice of an individualized therapeutic intervention for a patient with MF is a very complex issue and is dependent on several factors. The first factor being their overall prognosis with their illness (which can vary from a median of 2 years in high-risk patients to over 10 years in low-risk patients) and the potential impact of a therapeutic intervention not only on survival but also on quality of life. Current available therapies have been strictly palliative for disease-associated anemia and/or splenomegaly. At present, we have a new generation of inhibitors of JAK2 (Ruxolitinib, CYT387, SB1518, TG101348, with others in development), which have been shown to improve splenomegaly, improve symptomatic burden of illness and improve quality of life. In addition, these inhibitors of JAK2 may have an impact on the natural history of MF, but confirmation of the presence and degree of this impact is still pending. Clinical availability of JAK2 inhibitors may alter the timing of transplant in marginal transplant candidates (that is, those over the age of 60), may have a role preceding ASCT to improve spleen size and performance status before transplant and might be frontline therapy in intermediate and high-risk patients who are not candidates for ASCT.