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

The European LeukaemiaNet (ELN) measurable residual disease (MRD) working group have published consensus guidelines to standardise 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 of testing, and the subsequent interpretation of results, both crucial to patient safety. The majority of participants in this study were able to detect, accurately quantify and interpret MRD testing results correctly, with a level of proficiency expected from a clinical trial or standard of care setting. However, a number of 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 consequences clinically, committing patients to unneeded additional chemotherapy and/or transplant with the attendant risk of morbidity and mortality, and therefore highlights the need for ongoing external quality assessment (EQA)/proficiency testing (PT) 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.