The Clinical Utility of Mutation Testing in Acute Leukemia: A Canadian Consensus.

FMS-like tyrosine kinase 3 () mutations are detected in approximately 20-30% of patients with acute myeloid leukemia (AML), with the presence of a internal tandem duplication (-ITD) mutation being associated with an inferior outcome. Assessment of mutational status is now essential to define optimal upfront treatment in both newly diagnosed and relapsed AML, to support post-induction allogeneic hematopoietic stem cell transplantation (alloSCT) decision-making, and to evaluate treatment response via measurable (minimal) residual disease (MRD) evaluation. In view of its importance in AML diagnosis and management, the Canadian Leukemia Study Group/Groupe canadien d'étude sur la leucémie (CLSG/GCEL) undertook the development of a consensus statement on the clinical utility of mutation testing, as members reported considerable inter-center variability across Canada with respect to testing availability and timing of use, methodology, and interpretation. The CLSG/GCEL panel identified key clinical and hematopathological questions, including: (1) which patients should be tested for mutations, and when?; (2) which is the preferred method for mutation testing?; (3) what is the clinical relevance of -ITD size, insertion site, and number of distinct -ITDs?; (4) is there a role for analysis in MRD assessment?; (5) what is the clinical relevance of the -ITD allelic burden?; and (6) how should results of mutation testing be reported? The panel followed an evidence-based approach, taken together with Canadian clinical and laboratory experience and expertise, to create a consensus document to facilitate a more uniform approach to AML diagnosis and treatment across Canada.