Clearance of Driver Mutations after Transplantation for Myelofibrosis.

作者：N. Gagelmann, Marie Quarder, A. Badbaran, Kristin Rathje, D. Janson, C. Lück, Johanna Richter, F. Marquard, Sofia Oechsler, R. Massoud, E. Klyuchnikov, Ina Rudolph, Mathias Schäfersküpper, Christian Niederwieser, S. Heidenreich, Carolina Berger, B. Fehse, C. Wolschke, F. Ayuk, N. Kröger · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2408941 · 被引用次数：16 · 研究领域：Medicine

BACKGROUND Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for myelofibrosis. Driver mutations are the pathophysiological hallmark of the disease, but the role of mutation clearance after transplantation is unclear. METHODS We used highly sensitive polymerase-chain-reaction technology to analyze the dynamics of driver mutations in peripheral-blood samples from 324 patients with myelofibrosis (73% with JAK2 mutations, 23% with CALR mutations, and 4% with MPL mutations) who were undergoing transplantation after reduced-intensity conditioning. Mutations were detected before transplantation and at 30, 100, and 180 days after transplantation to measure clearance and its effect on relapse and cure. The two primary end points were relapse and disease-free survival. RESULTS At day 30 after transplantation, mutation clearance was found in 42% of the patients who had JAK2 mutations, 73% of those who had CALR mutations, and 54% of those who had MPL mutations; the corresponding percentages at day 100 were 63%, 82%, and 100%. The cumulative incidence of relapse at 1 year was 6% (95% confidence interval [CI], 2 to 10) among patients with mutation clearance at day 30 after transplantation and 21% (95% CI, 15 to 27) among those 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 those w...