Value of DNA sequencing pre-HCT for AML patients

Dillon LW, Gui G, Page KM, et al. DNA Sequencing to Detect Residual Disease in Adults with Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant. JAMA. 2023; 329 (9): 745 (doi: 10.1001/jama.2023.1363).

In patients with acute myeloid leukemia (AML) in first remission before undergoing allogeneic hematopoietic cell transplant, new research shows poorer outcomes for individuals with residual FLT3 internal tandem duplication (FLT3-ITD) or NPM1 DNA variants in the blood at an allele fraction of 0.01% or higher. The retrospective observational study performed DNA sequencing on pretransplant blood from 1,075 adult patients who had received their initial allogeneic hematopoietic cell transplant during their first complete remission for AML associated with variants in FLT3, NPM1, IDH1, IDH2, or KIT at one of 111 treatment sites. FLT3-ITD and/or NPM1 mutated AML were detected in 822 patients. Poorer outcomes after transplant were associated with persistent NPM1 and/or FLT3-ITD variants in the blood of 17.3% (64/371) of patients in the discovery cohort who were in remission prior to transplant between 2013 and 2017. In the validation cohort, 17.3% (78/451) of the patients with residual NPM1 and/or FLT3-ITD variants who had undergoing transplant in 2018-2019 had higher relapse rates (68% vs 21%) and lower survival (39% vs 63%) at 3 years. These findings indicate the need for additional research to learn whether outcomes for AML patients can benefit from routine DNA-sequencing testing for residual variants, the researchers concluded.

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Tags: AML, MRD, Patients, Cellular therapy, Allogeneic, hematopoietic, Transplant, translational, transplatation, measurable residual disease

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