Haematologica (Nov 2020)
Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: the PETHEMA NGS-AML project
- Claudia Sargas,
- Rosa Ayala,
- María Carmen Chillón,
- María J. Larráyoz,
- Estrella Carrillo-Cruz,
- Cristina Bilbao,
- Manuel Yébenes-Ramírez,
- Marta Llop,
- Inmaculada Rapado,
- Ramón García-Sanz,
- Iria Vázquez,
- Elena Soria,
- Yanira Florido-Ortega,
- Kamila Janusz,
- Carmen Botella,
- Josefina Serrano,
- David Martínez-Cuadrón,
- Juan Bergua,
- Mari Luz Amigo,
- Pilar Martínez-Sánchez,
- Mar Tormo,
- Teresa Bernal,
- Pilar Herrera-Puente,
- Raimundo García,
- Lorenzo Algarra,
- María J. Sayas,
- Lisette Costilla-Barriga,
- Esther Pérez-Santolalla,
- Inmaculada Marchante,
- Esperanza Lavilla-Rubira,
- Víctor Noriega,
- Juan M. Alonso-Domínguez,
- Miguel Á. Sanz,
- Joaquín Sánchez-Garcia,
- María T. Gómez-Casares,
- José A. Pérez-Simón,
- María J. Calasanz,
- Marcos González-Díaz,
- Joaquín Martínez-López,
- Eva Barragán,
- Pau Montesinos
Affiliations
- Claudia Sargas
- Molecular Biology Unit, Hospital Universitari i Politécnic-IIS La Fe, Valencia
- Rosa Ayala
- Hematology Department, Hospital Universitario 12 de Octubre, CNIO, Complutense University, Madrid
- María Carmen Chillón
- Hospital Universitario de Salamanca (HUS/IBSAL), CIBERONC and Center for Cancer Research-IBMCC (USAL-CSIC), Salamanca
- María J. Larráyoz
- CIMA LAB Diagnostics-Universidad de Navarra, Pamplona
- Estrella Carrillo-Cruz
- Hospital Universitario Virgen del Rocío, Instituto de Biomedicina (IBIS / CSIC / CIBERONC), Universidad de Sevilla, Sevilla
- Cristina Bilbao
- Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria
- Manuel Yébenes-Ramírez
- IMIBIC, Hematology, Hospital Universitario Reina Sofía, UCO, Córdoba
- Marta Llop
- Molecular Biology Unit, Hospital Universitari i Politécnic-IIS La Fe, Valencia
- Inmaculada Rapado
- Hematology Department, Hospital Universitario 12 de Octubre, CNIO, Complutense University, Madrid
- Ramón García-Sanz
- Hospital Universitario de Salamanca (HUS/IBSAL), CIBERONC and Center for Cancer Research-IBMCC (USAL-CSIC), Salamanca
- Iria Vázquez
- CIMA LAB Diagnostics-Universidad de Navarra, Pamplona
- Elena Soria
- Hospital Universitario Virgen del Rocío, Instituto de Biomedicina (IBIS / CSIC / CIBERONC), Universidad de Sevilla, Sevilla
- Yanira Florido-Ortega
- Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria
- Kamila Janusz
- IMIBIC, Hematology, Hospital Universitario Reina Sofía, UCO, Córdoba
- Carmen Botella
- Hospital General Universitario de Alicante, Alicante
- Josefina Serrano
- IMIBIC, Hematology, Hospital Universitario Reina Sofía, UCO, Córdoba
- David Martínez-Cuadrón
- Hematology Department, Hospital Universitari i Politécnic-IIS La Fe, Valencia, Spain; CIBERONC Instituto de Salud Carlos III, Madrid
- Juan Bergua
- Hospital Universitario San Pedro de Alcántara, Cáceres
- Mari Luz Amigo
- Hospital Universitario Morales Messeguer, Murcia
- Pilar Martínez-Sánchez
- Hematology Department, Hospital Universitario 12 de Octubre, CNIO, Complutense University, Madrid
- Mar Tormo
- Hematology Department, Hospital Clínico Universitario-INCLIVA, Valencia
- Teresa Bernal
- Hospital Universitario Central de Asturias, Oviedo
- Pilar Herrera-Puente
- Hospital Universitario Ramón y Cajal, Madrid
- Raimundo García
- Hospital Universitari General de Castelló, Castellón
- Lorenzo Algarra
- Hospital Universitario General de Albacete, Albacete
- María J. Sayas
- Hospital Universitari Dr. Peset, Valencia
- Lisette Costilla-Barriga
- Hospital Universitario Miguel Servet, Zaragoza
- Esther Pérez-Santolalla
- Hospital de Donosti, San Sebastián
- Inmaculada Marchante
- Hospital Universitario Puerta del Mar, Cádiz
- Esperanza Lavilla-Rubira
- Complexo Hospitalario Lucus Augusti, Lugo
- Víctor Noriega
- Complexo Hospitalario Universitario A Coruña, A Coruña
- Juan M. Alonso-Domínguez
- Hospital Universitario Fundación Jiménez Díaz, Madrid
- Miguel Á. Sanz
- Hematology Department, Hospital Universitari i Politécnic-IIS La Fe, Valencia, Spain; CIBERONC Instituto de Salud Carlos III, Madrid
- Joaquín Sánchez-Garcia
- IMIBIC, Hematology, Hospital Universitario Reina Sofía, UCO, Córdoba
- María T. Gómez-Casares
- Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria
- José A. Pérez-Simón
- Hospital Universitario Virgen del Rocío, Instituto de Biomedicina (IBIS / CSIC / CIBERONC), Universidad de Sevilla, Sevilla
- María J. Calasanz
- CIMA LAB Diagnostics-Universidad de Navarra, Pamplona
- Marcos González-Díaz
- Hospital Universitario de Salamanca (HUS/IBSAL), CIBERONC and Center for Cancer Research-IBMCC (USAL-CSIC), Salamanca
- Joaquín Martínez-López
- Hematology Department, Hospital Universitario 12 de Octubre, CNIO, Complutense University, Madrid
- Eva Barragán
- Molecular Biology Unit, Hospital Universitari i Politécnic-IIS La Fe, Valencia, Spain; CIBERONC Instituto de Salud Carlos III, Madrid
- Pau Montesinos
- Hematology Department, Hospital Universitari i Politécnic-IIS La Fe, Valencia, Spain; CIBERONC Instituto de Salud Carlos III, Madrid
- DOI
- https://doi.org/10.3324/haematol.2020.263806
- Journal volume & issue
-
Vol. 106,
no. 12
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 clinical routine raises new challenges focused on the diversity of assays and variant reporting criteria. In order to overcome this challenge, the PETHEMA 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 conditions across laboratories. After consensus of relevant genes and optimization 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 laboratories 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).