AUTHOR=Vega-García Nerea , Perez-Jaume Sara , Esperanza-Cebollada Elena , Vicente-Garcés Clara , Torrebadell Montserrat , Jiménez-Velasco Antonio , Ortega Margarita , Llop Marta , Abad Lorea , Vagace José Manuel , Minguela Alfredo , Pratcorona Marta , Sánchez-Garcia Joaquín , García-Calderón Clara B. , Gómez-Casares María Teresa , Martín-Clavero Estela , Escudero Adela , Riñón Martinez-Gallo Marta , Muñoz Luz , Velasco María Rosario , García-Morin Marina , Català Albert , Pascual Antonia , Velasco Pablo , Fernández José Mª. , Lassaletta Alvaro , Fuster José Luis , Badell Isabel , Molinos-Quintana Águeda , Molinés Antonio , Guerra-García Pilar , Pérez-Martínez Antonio , García-Abós Miriam , Robles Ortiz Reyes , Pisa Sandra , Adán Rosa , Díaz de Heredia Cristina , Dapena José Luis , Rives Susana , Ramírez-Orellana Manuel , Camós Mireia 

TITLE=Measurable Residual Disease Assessed by Flow-Cytometry Is a Stable Prognostic Factor for Pediatric T-Cell Acute Lymphoblastic Leukemia in Consecutive SEHOP Protocols Whereas the Impact of Oncogenetics Depends on Treatment

JOURNAL=Frontiers in Pediatrics

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.614521

DOI=10.3389/fped.2020.614521

ISSN=2296-2360

ABSTRACT=<p>Robust and applicable risk-stratifying genetic factors at diagnosis in pediatric T-cell acute lymphoblastic leukemia (T-ALL) are still lacking, and most protocols rely on measurable residual disease (MRD) assessment. In our study, we aimed to analyze the impact of <italic>NOTCH1, FBXW7, PTEN</italic>, and <italic>RAS</italic> mutations, the measurable residual disease (MRD) levels assessed by flow cytometry (FCM-MRD) and other reported risk factors in a Spanish cohort of pediatric T-ALL patients. We included 199 patients treated with SEHOP and PETHEMA consecutive protocols from 1998 to 2019. We observed a better outcome of patients included in the newest SEHOP-PETHEMA-2013 protocol compared to the previous SHOP-2005 cohort. FCM-MRD significantly predicted outcome in both protocols, but the impact at early and late time points differed between protocols. The impact of FCM-MRD at late time points was more evident in SEHOP-PETHEMA 2013, whereas in SHOP-2005 FCM-MRD was predictive of outcome at early time points. Genetics impact was different in SHOP-2005 and SEHOP-PETHEMA-2013 cohorts: <italic>NOTCH1</italic> mutations impacted on overall survival only in the SEHOP-PETHEMA-2013 cohort, whereas homozygous deletions of <italic>CDKN2A</italic>/<italic>B</italic> had a significantly higher CIR in SHOP-2005 patients. We applied the clinical classification combining oncogenetics, WBC count and MRD levels at the end of induction as previously reported by the FRALLE group. Using this score, we identified different subgroups of patients with statistically different outcome in both Spanish cohorts. In SHOP-2005, the FRALLE classifier identified a subgroup of high-risk patients with poorer survival. In the newest protocol SEHOP-PETHEMA-2013, a very low-risk group of patients with excellent outcome and no relapses was detected, with borderline significance. Overall, FCM-MRD, WBC count and oncogenetics may refine the risk-stratification, helping to design tailored approaches for pediatric T-ALL patients.</p>