Assessment of acute myeloid leukemia molecular measurable residual disease testing in an interlaboratory study

Abstract

The European LeukaemiaNet (ELN) measurable residual disease (MRD) working group has published consensus guidelines to standardize molecular genetic MRD testing of the t(8;21)(q22;q22.1) RUNX1::RUNX1T1, inv(16)(p13.1q22) CBFB::MYH11, t(15;17)(q24.1;q21.2) PML::RARA, and NPM1 type A markers. A study featuring 29 international laboratories was performed to assess interlaboratory variation in testing and the subsequent interpretation of results, both crucial to patient safety. Most participants in this study were able to detect, accurately quantify, and correctly interpret MRD testing results, with a level of proficiency expected from a clinical trial or standard-of-care setting. However, a few testing and interpretive errors were identified that, in a patient setting, would have led to misclassification of patient outcomes and inappropriate treatment pathways being followed. Of note, a high proportion of participants reported false-positive results in the NPM1 marker-negative sample. False-positive results may have clinical consequences, committing patients to unneeded additional chemotherapy and/or transplant with the attendant risk of morbidity and mortality, which therefore highlights the need for ongoing external quality assessment/proficiency testing in this area. Most errors identified in the study were related to the interpretation of results. It was noted that the ELN guidance lacks clarity for certain clinical scenarios and highlights the requirement for urgent revision of the guidelines to elucidate these issues and related educational efforts around the revisions to ensure effective dissemination.