Page 59 - 2021_12-Haematologica-web

Acute Myeloid Leukemia
Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: the PETHEMA NGS-AML project
Claudia Sargas,1 Rosa Ayala,2 María Carmen Chillón,3 María J. Larráyoz,4 Estrella Carrillo-Cruz,5 Cristina Bilbao,6 Manuel Yébenes-Ramírez,7 Marta Llop,1 Inmaculada Rapado,2 Ramón García-Sanz,3 Iria Vázquez,4 Elena Soria,5 Yanira Florido-Ortega,6 Kamila Janusz,7 Carmen Botella,8 Josefina Serrano,7 David Martínez-Cuadrón,9,10 Juan Bergua,11 Mari Luz Amigo,12 Pilar Martínez-Sánchez,2 Mar Tormo,13 Teresa Bernal,14 Pilar Herrera-Puente,15 Raimundo García,16 Lorenzo Algarra,17 María J. Sayas,18 Lisette Costilla-Barriga,19 Esther Pérez-Santolalla,20 Inmaculada Marchante,21 Esperanza Lavilla-Rubira,22 Víctor Noriega,23 Juan M. Alonso-Domínguez,24 Miguel Á. Sanz,9,10 Joaquín Sánchez-Garcia,7 María T. Gómez-Casares,6 José A. Pérez-Simón,5 María J. Calasanz,4 Marcos González- Díaz,3 Joaquín Martínez-López,2 Eva Barragán,1,10# and Pau Montesinos,9,10# on behalf of the PETHEMA group
1Molecular Biology Unit, Hospital Universitari i Politècnic-IIS La Fe, Valencia; 2Hematology Department, Hospital Universitario 12 de Octubre, CNIO, Complutense University, Madrid; 3Hospital Universitario de Salamanca (HUS/IBSAL), CIBERONC and Center for Cancer Research-IBMCC (USAL/CSIC), Salamanca; 4CIMA LAB Diagnostics-Universidad de Navarra, Pamplona; 5Hospital Universitario Virgen del Rocío, Instituto de Biomedicina (IBIS/CSIC/CIBERONC), Universidad de Sevilla, Sevilla; 6Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria; 7IMIBIC, Hematology, Hospital Universitario Reina Sofía, UCO, Córdoba; 8Hospital General Universitario de Alicante, Alicante; 9Hematology Department, Hospital Universitari i Politécnic-IIS La Fe, Valencia; 10CIBERONC Instituto de Salud Carlos III, Madrid; 11Hospital Universitario San Pedro de Alcántara, Cáceres; 12Hospital Universitario Morales Messeguer, Murcia; 13Hematology Department, Hospital Clínico Universitario-INCLIVA, Valencia; 14Hospital Universitario Central de Asturias, Oviedo; 15Hospital Universitario Ramón y Cajal, Madrid; 16Hospital Universitari General de Castelló, Castellón; 17Hospital Universitario General de Albacete, Albacete; 18Hospital Univerisitario Dr. Peset, Valencia; 19Hospital Universitario Miguel Servet, Zaragoza; 20Hospital de Donosti, San Sebastián; 21Hospital Universitario Puerta del Mar, Cádiz; 22Complexo Hospitalario Lucus Augusti, Lugo; 23Complexo Hospitalario Universitario A Coruña, A Coruña and 24Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
#EB and PM contributed equally as co-senior authors.
ABSTRACT
Next-generation sequencing (NGS) has recently been introduced to efficiently and simultaneously detect genetic variations in acute myeloid leukemia (AML). However, its implementation in the clin- ical routine raises new challenges focused on the diversity of assays and variant reporting criteria. In order to overcome this challenge, the PETHE- MA group established a nationwide network of reference laboratories aimed to deliver molecular results in the clinics. We report the technical cross-validation results for NGS panel genes during the standardization process and the clinical validation in 823 samples of 751 patients with newly diagnosed or refractory/relapse AML. Two cross-validation rounds were performed in seven nationwide reference laboratories in order to reach a consensus regarding quality metrics criteria and variant reporting. In the pre-standardization cross-validation round, an overall concordance of 60.98% was obtained with a great variability in selected genes and con- ditions across laboratories. After consensus of relevant genes and opti- mization of quality parameters the overall concordance rose to 85.57% in the second cross-validation round. We show that a diagnostic network with harmonized NGS analysis and reporting in seven experienced labo- ratories is feasible in the context of a scientific group. This cooperative nationwide strategy provides advanced molecular diagnostic for AML patients of the PETHEMA group (clinicaltrials gov. Identifier: NCT03311815).
Ferrata Storti Foundation
Haematologica 2021 Volume 106(12):3079-3089
Correspondence:
EVA BARRAGÁN GONZÁLEZ
barragan_eva@gva.es
Received: June 24, 2020.
Accepted: November 3, 2020. Pre-published: November12,2020.
https://doi.org/10.3324/haematol.2020.263806 ©2021 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2021; 106(12)
3079
ARTICLE