Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been the only treatment option for acute myeloid leukemia (AML) refractory to induction chemotherapy, with only 10–20% of patients achieving long-term survival. Certain donor genotypes may confer leukemia-clearing effects after allo-HSCT. We performed whole-exome sequencing of five pairs of the germ lines in AML patients who achieved long-term remission after allo-HSCT and in their donors, and found two significant variants: EGFR c.2982C > T and CDH11 c.945G > A. To validate the protective effects of these leukemia-clearing genotypes (LCGs), AML patients who received allo-HSCT in a complete-remission status were also analyzed. Twenty-two of 96 donors (22.9%) had LCGs in their genomes, and overall survival was significantly longer in patients who received allo-HSCT from donors with germ-line LCGs (hazard ratio=0.47, 95% confidence interval=0.24–0.94, p = .033). These findings indicate that donor germ-line LCGs have phenotypically leukemia-clearing effects and are biomarkers for predicting clinical outcomes in allogeneic transplantation in AML patients.
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