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.

• Authors: Vikas Gupta, Parameswaran Hari, Ronald Hoffman
• Journal: Blood (Blood) Vol. 120 Issue 7 Pg. 1367-79 (Aug 16 2012) ISSN: 1528-0020 [Electronic] United States
• PMID: 22700718 (Publication Type: Journal Article, Review)

Chemical References

• Protein Kinase Inhibitors
• Janus Kinase 1

Topics

• Hematopoietic Stem Cell Transplantation
• Humans
• Janus Kinase 1 (antagonists & inhibitors)
• Primary Myelofibrosis (drug therapy)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Transplantation, Homologous
• Treatment Outcome