Researchers used next generation sequencing (NGS) of 26 genes and found mutations in TP53, WT1 and FLT3-ITD were associated with an increased risk of acute myeloid leukemia (AML) relapse after hematopoietic cell transplantation (HCT) (adjusted Hazard Ratio [aHR] 2.90, p=0.009; aHR 2.51, p=0.02; and aHR 1.83, p=0.07, respectively). In addition, a DNMT3A mutation in the absence of FLT3-ITD and NPM1 mutations was associated with a significantly lower relapse risk (aHR 0.22, p=0 04).
Further analysis revealed that 86% (96/112) of patients had at least one pathogenic mutation associated with post-transplant relapse. Six patients in the study had NGS performed both pre-transplant and at the time of relapse, and in all 6 patients there was evidence for clonal evolution.
The researchers note that pre-transplant testing can be used to guide treatment options and because clonal evolution is present at post-allogeneic HCT relapse, repeat genetic profiling is a useful tool to reveal acquired mutations that may require treatment modifications.