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The Clinical Utility of <i>FLT3</i> Mutation Testing in Acute Leukemia: A Canadian Consensus
oleh: Julie Bergeron, Jose-Mario Capo-Chichi, Hubert Tsui, Etienne Mahe, Philip Berardi, Mark D. Minden, Joseph M. Brandwein, Andre C. Schuh
Format: | Article |
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Diterbitkan: | MDPI AG 2023-12-01 |
Deskripsi
FMS-like tyrosine kinase 3 (<i>FLT3</i>) mutations are detected in approximately 20–30% of patients with acute myeloid leukemia (AML), with the presence of a <i>FLT3</i> internal tandem duplication (<i>FLT3</i>-ITD) mutation being associated with an inferior outcome. Assessment of <i>FLT3</i> 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 <i>FLT3</i> 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 <i>FLT3</i> mutations, and when?; (2) which is the preferred method for <i>FLT3</i> mutation testing?; (3) what is the clinical relevance of <i>FLT3</i>-ITD size, insertion site, and number of distinct <i>FLT3</i>-ITDs?; (4) is there a role for <i>FLT3</i> analysis in MRD assessment?; (5) what is the clinical relevance of the <i>FLT3</i>-ITD allelic burden?; and (6) how should results of <i>FLT3</i> 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.