FROM NEJM JOURNAL WATCH: July 3, 2014
Stem-Cell Transplantation for Middle-Aged Patients with Myelofibrosis
David Green, MD, PhD Reviewing Rondelli D et al., Blood 2014 Jun 24;
The benefits of allogeneic hematopoietic stem-cell transplantation outweigh the risks, but only with sibling donors.
Myelofibrosis is a progressive disease that culminates in fatal cytopenias or leukemic transformation. The only curative therapy is allogeneic hematopoietic stem-cell transplantation (AHSCT), but the feasibility of this approach in older patients has been unclear.
To examine the safety and effectiveness of reduced-intensity AHSCT in this setting, investigators conducted a prospective, multicenter, phase II study involving 66 patients with primary myelofibrosis (median age, 55; range 30–65; about half had JAK2 V617F mutation); 32 had sibling donors, and 34 had unrelated donors. All patients received fludarabine and melphalan for conditioning. Those receiving grafts from unrelated donors also received rabbit antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate.
Neutrophil and platelet engraftment occurred in 97% and 88%, respectively, of the sibling-donor group, but in only 76% and 59% of the unrelated-donor group. The overall graft-failure rate was 6% with sibling grafts and 36% with unrelated-donor grafts. Approximately 40% of all patients had acute GVHD, and about a third had chronic GVHD. At a median follow-up of 25 months, significantly more patients with sibling grafts than with unrelated-donor grafts were alive (75% vs. 32%; P<0.001); 59% of the deaths in the unrelated-donor group were due to transplant-related complications.
The overall response rate in the 46 patients who survived at least 180 days was 93% in the sibling group and 69% in the unrelated donor group. The median event-free survival had not been reached in the former, but was only 6 months (95% confidence interval, 2–25) in the latter, and these patients also had a trend toward a worse survival if they had the JAK2 mutation or a higher-risk clinical stage (intermediate-2 or high risk).
This study demonstrates that reduced-intensity AHSCT achieves clinical responses in middle-aged patients with myelofibrosis, but the benefit outweighs the risk only if the stem cells are obtained from matched-sibling donors. Whether pretreatment with JAK2 inhibitors will broaden the indications for AHSCT is currently under investigation.