FLT3-ITD in Children with Early T-cell Precursor (ETP) Acute Lymphoblastic Leukemia: Incidence and Potential Target for Monitoring Minimal Residual Disease (MRD)

Early T‐cell precursor (ETP) is an aggressive form of acute lymphoblastic leukemia (ALL), associated with high risk of relapse. This leukemia subtype shows a higher prevalence of mutations, typically associated with acute myeloid leukemia (AML), including RAS and FLT3 mutations. FLT3‐ ITD was identified in 35% cases of adult ETP‐ALL, but data in the pediatric counterpart are lacking. ETPs frequently lack immunoglobulin (IG) and T‐cell receptor (TR) gene rearrangements, used for minimal residual disease (MRD) monitoring. Among 718 T‐ALL enrolled in Italy into AIEOP‐BFM‐ ALL2000, AIEOP‐ALLR2006, and AIEOP‐BFM‐ALL2009 consecutive protocols, 86 patients (12%) were identified as ETP and 77 out of 86 children were studied for the presence of FLT3‐ITD. A total of 10 out of 77 (13%) ETP cases were FLT3‐ITD positive. IG/TR MRD monitoring was feasible only in four cases. FLT3‐ITD MRD monitoring was performed using real‐time PCR in all FLT3‐ITD positive ETP cases. A comparison between IG/TR and FLT3‐ITD resulted in comparable findings. Our study demonstrated that the FLT3‐ITD prevalence in children was lower (13%) than that reported in adult ETP‐ALL. FLT3‐ITD can be used as a marker for sensitive molecular MRD monitoring in ETP‐ALL when IG/TR markers are not available, potentially selecting those patients who should spare allogeneic hematopoietic stem cell transplantation (HSCT). Finally, the FLT3 pathway is a robust druggable target in this aggressive form of leukemia.