A study from the University of California San Diego suggests that genetic testing after stem cell transplantation could help identify patients with acute myeloid leukemia (AML) who are most likely to relapse, potentially allowing earlier intervention. The findings, presented Friday at the Association for Molecular Pathology (AMP) annual meeting in Boston, indicate that residual gene mutations detected after transplant strongly correlate with recurrence risk.
The research team, led by Wei Song, MD, PhD, and Forough Sargolzaeiaval, MD, of the University of California San Diego, analyzed 115 patients with AML who underwent allogeneic hematopoietic cell transplantation (HCT) at UC San Diego Medical Center between 2017 and 2024. Of these, 74 patients had complete next-generation sequencing (NGS) data available at 3 time points: diagnosis, after chemotherapy, and following transplant.
Across those patients, the investigators identified 181 mutations spanning 52 genes. Post-transplant mutations were detected in 35 patients, 31 of whom later relapsed. Two genes, TET2 and DNMT3A, showed the strongest association with recurrence. Patients with detectable post-transplant mutations in these genes had markedly higher odds of relapse (OR 3.35 and 1.97, respectively).
Conversely, patients whose donor cells had fully replaced their own marrow—achieving high donor chimerism—tended to remain in remission, even if low-level mutations persisted. These lingering variants may represent clonal hematopoiesis of indeterminate potential (CHIP) rather than residual leukemia, the researchers noted.
Mutation burden after transplant was inversely correlated with donor chimerism (P=.034), and the presence of detectable mutations following HCT was associated with a more than fourfold increase in relapse risk (HR 4.34; P=.003). Older age also trended toward worse outcomes.
The results suggest that integrating NGS-based mutation profiling with chimerism assessment can improve post-transplant risk stratification, which could help clinicians decide when closer follow-up or preemptive therapy might be warranted.
