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
Vega-García, N. (Institut de Recerca Sant Joan de Déu)
Perez-Jaume, S. (Institut de Recerca Sant Joan de Déu)
Esperanza-Cebollada, Elena (Institut de Recerca Sant Joan de Déu)
Vicente-Garcés, C. (Institut de Recerca Sant Joan de Déu)
Torrebadell, M. (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Jiménez-Velasco, Antonio (Hospital Regional Universitario Carlos Haya (Málaga))
Ortega, M. (Hospital Universitari Vall d'Hebron)
Llop, M. (Centro de Investigación Biomédica en Red de Cáncer)
Abad, Lorea (Hospital Infantil Universitario Niño Jesús (Madrid))
Vagace, J.M. (Hospital Materno Infantil)
Minguela, A. (Instituto Murciano de Investigación Biosanitaria)
Pratcorona, Marta (Institut d'Investigació Biomèdica Sant Pau)
Sánchez-Garcia, J. (Instituto Maimónides de Investigación Biomédica de Córdoba)
García-Calderón, C.B. (Instituto de Biomedicina de Sevilla)
Gómez-Casares, M.T. (Hospital Universitario de Gran Canaria Dr. Negrín)
Martín-Clavero, E. (Hospital Universitario)
Escudero, A. (Instituto de Investigación Sanitaria del Hospital Universitario La Paz)
Riñón Martinez-Gallo, M. (Hospital Universitario de Cruces (Barakaldo, País Basc))
Muñoz, L. (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Velasco, M.R. (Haematology Department. Hospital Virgen de la Salud)
García-Morin, M. (Hospital General Universitario Gregorio Marañón)
Català, Albert (Institut de Recerca Sant Joan de Déu)
Pascual, A. (Hospital Regional Universitario Carlos Haya (Málaga))
Velasco, P. (Hospital Universitari Vall d'Hebron)
Fernández, J.M. (Hospital Universitari i Politècnic La Fe (València))
Lassaletta, Álvaro (Hospital Infantil Universitario Niño Jesús (Madrid))
Fuster, José Luis (Instituto Murciano de Investigación Biosanitaria)
Badell Serra, Isabel (Institut d'Investigació Biomèdica Sant Pau)
Molinos-Quintana, Á. (Instituto de Biomedicina de Sevilla)
Molinés, A. (H.U. Materno Infantil de Canarias)
Guerra-García, P. (Hospital Universitario La Paz (Madrid))
Pérez-Martínez, Antonio (Hospital Universitario La Paz (Madrid))
García-Abós, M. (Hospital de Donostia (Sant Sebastià, País Basc))
Robles Ortiz, R. (Complejo Hospitalario de Navarra)
Pisa, S. (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Adán, R. (Hospital Universitario de Cruces (Barakaldo, País Basc))
Díaz de Heredia, Cristina (Hospital Universitari Vall d'Hebron)
Dapena, José Luis (Institut de Recerca Sant Joan de Déu)
Rives, S. (Institut de Recerca Sant Joan de Déu)
Ramírez-Orellana, M. (Hospital Infantil Universitario Niño Jesús (Madrid))
Camós, Mireia (Centro de Investigación Biomédica en Red de Enfermedades Raras)

Date:	2021
Abstract:	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 NOTCH1, FBXW7, PTEN, and RAS 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: NOTCH1 mutations impacted on overall survival only in the SEHOP-PETHEMA-2013 cohort, whereas homozygous deletions of CDKN2A/B 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.
Grants:	Instituto de Salud Carlos III PI12/02417 Instituto de Salud Carlos III PI16/00246
Note:	Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Measurable (minimal) residual disease ; T-cell acute lymphoblastic leukemia ; Oncogenetics ; NOTCH1 ; Flow cytometry ; Pediatrics ; Risk-factors
Published in:	Frontiers in Pediatrics, Vol. 8 (february 2021) , p. 614521, ISSN 2296-2360

DOI: 10.3389/fped.2020.614521
PMID: 33614543

12 p, 659.9 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles