The absence of cancer-related mutations 30 days after a transplant in patients with myelofibrosis might be more effective in measuring treatment response than traditional donor chimerism, according to research published in The New England Journal of Medicine.
“In patients with myelofibrosis, clearance of driver mutations at day 30 after transplantation appeared to influence relapse and survival, irrespective of the underlying driver mutation,” the researchers, led by Nico Gagelmann, MD, of the Department of Stem Cell Transplantation at the University Medical Center Hamburg-Eppendorf in Germany, wrote in the paper.
According to the authors of the study, their research was prompted by the fact that the role of mutation clearance in predicting long-term outcomes like relapse and survival had not been previously investigated, despite the fact that driver mutations are the pathophysiological hallmark of myelofibrosis.
Using polymerase-chain-reaction, Dr. Gagelmann and colleagues analyzed the peripheral-blood samples from 324 patients with myelofibrosis (TABLE 1) who were undergoing transplantation. The researchers measured patient mutation before transplantation, and at 30, 100, and 180 days after patients had undergone a transplant.
At 30 days post-transplant, mutation clearance was seen in 42% of patients with JAK2 mutations, 73% with CALR, and 54% with MPL, improving by day 100. Patients with clearance at day 30 had a 6% relapse rate at one year, compared to 21% without clearance. Six-year survival was also higher, with 61% disease-free and 74% overall survival for those with clearance, versus 41% and 60% for those without.
“Mutation clearance at day 30 appeared to outperform traditional donor chimerism as a measure of response; it was independently associated with a reduced risk of relapse or progression,” the researchers wrote.
Reference
Gagelmann N, Quarder M, Badbaran A, et al. Clearance of driver mutations after transplantation for myelofibrosis. N Engl J Med. 2025;392(2):150-160. doi:10.1056/NEJMoa2408941
