Retrospective analysis of relapse and disease-free survival associations with clearance of driver mutations after transplantation for myelofibrosis

Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for myelofibrosis (MF). Driver mutations are the pathophysiological hallmark of the disease, but the role of mutation clearance after transplantation is unclear. A retrospective study at the University Medical Center Hamburg-Eppendorf (Germany) included 324 MF patients (73% with JAK2 mutations, 23% with CALR mutations, and 4% with MPL mutations) who underwent transplantation. At day 30 after transplantation, mutation clearance was found in 42% of the patients with JAK2 mutations, 73% of the patients with CALR mutations, and 54% of the patients with MPL mutations. The cumulative incidence of relapse at 1 year was 6% (95% CI 2-10) among patients with mutation clearance at day 30 after transplantation and 21% (15-27) among patients without mutation clearance at day 30. Disease-free and overall survival at 6 years were 61% and 74%, respectively, among patients with mutation clearance at day 30 after transplantation, and 41% and 60%, respectively, among patients without mutation clearance at day 30. Mutation clearance at day 30 was independently associated with reduced risk of relapse or progression (HR 0.36; 95% CI 0,21-0,61) irrespective of the type or driver mutation. The authors conclude that in MF patients, clearance of driver mutations at day 30 after transplantation appeared to influence relapse and survival.