Allogeneic hematopoietic cell transplantation for myelofibrosis in the era of JAK inhibitors

Abstract

The discovery of JAK2617F mutation paved the way for the development of small molecule inhibitors of JAK1/2 resulting in first approved JAK1/2 inhibitor, ruxolitinib, for the treatment of patients with myelofibrosis (MF). Although JAK1/2 inhibitor therapy is effective in decreasing the burden of symptoms associated with splenomegaly and MF-related constitutional symptoms, it is neither curative nor effective in reducing the risk of leukemic transformation. Presently, allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for MF. A significant risk of regimen-related toxicities, graft failure, and GVHD are major barriers to the success of HCT in MF. Because of significant HCT-associated morbidity and mortality, divergent opinions regarding its appropriate role in this clinical situation have emerged. In this review, the risk-benefit ratios of modern drug therapy compared with HCT in MF patients are analyzed. A risk-adapted approach individualized to each patient's biologic characteristics and comorbidities is described, which is currently warranted in determining optimal treatment strategies for patients with MF. Inclusion of JAK1/2 inhibitor therapy in future transplant conditioning regimens may provide an opportunity to overcome some of these barriers, resulting in greater success with HCT for MF patients.

Figure 1

CIBMTR reporting trends showing transplant activity in myelofibrosis. (A) Based on age and graft source. (B) Based on donor type.

Figure 2

Suggested algorithm for approach to selection of first-line therapy (drug therapy vs HCT). (A) Low/Intermediate-1 risk MF. (B) Intermediate-2/High risk MF.

Figure 3

Aids to decision making in selection of initial therapy (drug therapy vs HCT) in patients with MF.