Rapid molecular screening of adult AML: Experience from the Spanish CETLAM cooperative group.

Abstract

Genetic testing is essential for risk stratification and early therapeutic decision-making in acute myeloid leukaemia (AML). While 2022 European LeukemiaNet (ELN) guidelines recommend a 3-5-day turnaround time for key molecular markers, next-generation sequencing (NGS) often extends to 15 days in clinical practice. In this study, we evaluated the first-year results of a centralized rapid screening platform for 15 hospitals in the Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias (CETLAM) cooperative group, modelled after the German-Austrian Acute Myeloid Leukaemia Study Group (AMLSG) diagnostic strategy. We prospectively enrolled 211 consecutive adult patients with de novo AML. A centralized laboratory performed nucleic acid purification, biobanking and high-priority molecular analysis including nucleophosmin 1 (NPM1), Fms-like tyrosine kinase 3 (FLT3-ITD/TKD), CCAAT enhancer binding protein alpha (CEBPA), isocitrate dehydrogenase 1 and 2 (IDH1/2), lysine methyltransferase 2A (KMT2A-PTD), upstream binding transcription factor (UBTF-TD) and 10 key fusions using polymerase chain reaction (PCR) and capillary electrophoresis. Results were compared with local NGS and cytogenetics to assess diagnostic accuracy and ELN risk reclassification. The mean analytical turnaround time was 3-4 days for high-priority mutations and 7 days for gene fusions. Initial rapid screening accurately identified 98% of favourable-risk cases. However, 74% of patients initially classified as intermediate-risk were reclassified as adverse-risk upon integration of NGS and cytogenetics. This CETLAM initiative demonstrates that a centralized molecular platform is a feasible and reliable strategy for early risk stratification and therapeutic decision-making in AML within a multicentre setting.