Impact of Genetic Factors at Diagnosis on HCT in Older AML Patients

Murdock HM, Kim HT, Denlinger N, et al. Impact of Diagnostic Genetics on Remission MRD and Transplantation Outcomes in Older AML Patients. Blood. 2022; (doi: 10.1182/blood.2021014520).

Clinical and genetic factors evident at diagnosis, rather than mutations encountered during remission, are drivers of older acute myeloid leukemia (AML) patients' measurable residual disease (MRD) response to allogeneic hematopoietic cell transplantation (HCT). Researchers conducted targeted mutational analysis on diagnostic samples from 295 AML patients age 60 years or older who underwent HCT in first complete remission. Ninety-one percent underwent reduced-intensity conditioning, and 192 patients underwent duplex sequencing at the time of remission. Before transplantation, persistent baseline mutations were present in 79.7% of patients, including 18.3% with only DNMT3A or TET2 mutations (DT) and 61.4% with other mutations (MRDpositive). MRD-positivity correlated with greater relapse and lower leukemia-free survival (LFS) than with DT and (MRDnegative) patients in univariable analysis. Multivariable assessment that factored in baseline risk showed that MRD-positivity had no independent effect on LFS, probably on account of its close affinity with diagnostic genetic properties such as MDS-associated gene mutations, TP53 mutations, and high-risk karyotype. Alternative approaches are needed to mitigate MRD-associated relapse risk.

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