title: The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose-intensive chemotherapy including rituximab.
abstract: The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma (BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose-Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array-based comparative genomic hybridization (CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next-generation sequencing (NGS). Ninety-seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy (P = 0·038), shorter progression-free survival (PFS; P = 0·007) and overall survival (OS; P = 0·009). The integrative analysis of array-CGH and NGS showed that 26·3% (5/19) and 36·8% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS (P = 0·011) while TCF3 alterations were associated with shorter OS (P = 0·032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol.
authors.affiliation: Cancer Research Centre, IBSAL, IBMCC, University of Salamanca, CSIC, Salamanca, Spain.|School of Biological Sciences (GEBIMOL), Pedagogical and Technological University of Colombia (UPTC), Colombia, IN, USA.
authors.forename: Maribel
authors.initials: M
authors.lastname: Forero-Castro
authors.affiliation: Cancer Research Centre, IBSAL, IBMCC, University of Salamanca, CSIC, Salamanca, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Robledo
authors.affiliation: Cancer Research Centre, IBSAL, IBMCC, University of Salamanca, CSIC, Salamanca, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Lumbreras
authors.affiliation: Cancer Research Centre, IBSAL, IBMCC, University of Salamanca, CSIC, Salamanca, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Benito
authors.affiliation: Cancer Research Centre, IBSAL, IBMCC, University of Salamanca, CSIC, Salamanca, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Hernández-Sánchez
authors.affiliation: Cancer Research Centre, IBSAL, IBMCC, University of Salamanca, CSIC, Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Hernández-Sánchez
authors.affiliation: Studies Institute of Health Sciences of Castilla and León (IESCYL), Salamanca, Spain.
authors.forename: Juan L
authors.initials: JL
authors.lastname: García
authors.affiliation: Haematology Department, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Corchete-Sánchez
authors.affiliation: Haematology Department, Clinical University Hospital of Valencia, Valencia, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
authors.affiliation: Haematology Department, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Barba
authors.affiliation: Pathology Department, Gregorio Marañón Hospital, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Menárguez
authors.affiliation: Clinical Haematology Department ICO-Hospital Germans Trias i Pujol, Jose Carreras Research Institute, Badalona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Ribera
authors.affiliation: Haematology Department, University Hospital October 12, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Grande
authors.affiliation: Haematology Department, University Hospital of Tarragona Joan XXIII, Tarragona, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Escoda
authors.affiliation: Haematology Department, General Hospital of Segovia, Segovia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Olivier
authors.affiliation: Haematology Department, University Hospital Virgen del Rocío, Seville, Spain.
authors.forename: Estrella
authors.initials: E
authors.lastname: Carrillo
authors.affiliation: Haematology Department, Clinical University Hospital of Valladolid, Valladolid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: García de Coca
authors.affiliation: Clinical Haematology Department ICO-Hospital Germans Trias i Pujol, Jose Carreras Research Institute, Badalona, Spain.
authors.forename: Josep-María
authors.initials: JM
authors.lastname: Ribera
authors.affiliation: Cancer Research Centre, IBSAL, IBMCC, University of Salamanca, CSIC, Salamanca, Spain.|Haematology Department, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Hernández-Rivas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000069283:Rituximab / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000069283:Rituximab
keywords: Burkitt lymphoma; array-based comparative genomic hybridization (aCGH); next-generation sequencing; outcome; rituximab