Utility of Repeated NGS Testing in Myeloid Diagnostic Work Up

Abstract

Abstract Introduction/Objective NGS is an integral component of diagnostic work-up of myeloid neoplasms, commonly applied at initial diagnosis and for assessment of treatment response. It is less clear how NGS should be repeated at disease follow-up when initial result is negative. In order to assess the utility of repeated NGS testing, we retrospectively analyzed results in patients with multiple tests. Methods/Case Report Myeloid NGS results were collected between 10/2017 and 4/2022 at University of Miami. The results were grouped by patients and arranged by collection date and finding of mutations. First, we identified patients with negative result or a single mutation of common CHIP gene TET2, DNMT3A, or ASXL1 (DAT) in the first available NGS test. Then we divided these patients into negative follow-up group, if all NGS results were the same as the initial test, and positive follow-up group, if any new mutations were detected. The NGS findings were correlated with clinical history and pathology diagnosis. Results (if a Case Study enter NA) Results from 876 patients were analyzed. A total of 362 patients underwent multiple NGS tests; among them, 84 were negative and 14 had a single DAT mutation in the first NGS test. Among the 98 patients, 21 (21.4%) were in the positive follow-up group, with median time-to-positive at 132 days; the other were in the negative follow-up group with median follow-up time at 258 days. Analysis of the patient history showed the positive follow-up group consists 16 patients who were in remission of high-grade myeloid neoplasm at the time of initial testing and relapsed at the time of detection of mutations, 4 patients who acquired alteration of uncertain significance after hematopoietic stem cell transplant, and 1 patient who acquired KRAS mutation corresponding to MDS developed 846 days after the initial testing. Conclusion Positive conversion in repeated NGS testing are mostly associated with relapsed myeloid neoplasm after chemotherapy.