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Title: The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose-intensive chemotherapy including rituximab.
Authors: Forero-Castro, Maribel
Robledo, Cristina
Lumbreras, Eva
Benito, Rocio
Hernández-Sánchez, Jesús M
Hernández-Sánchez, María
García, Juan L
Corchete-Sánchez, Luis A
Tormo, Mar
Barba, Pere
Menárguez, Javier
Ribera, Jordi
Grande, Carlos
Escoda, Lourdes
Olivier, Carmen
Carrillo, Estrella
García de Coca, Alfonso
Ribera, Josep-María
Hernández-Rivas, Jesús M
Keywords: Burkitt lymphoma;array-based comparative genomic hybridization (aCGH);next-generation sequencing;outcome;rituximab
metadata.dc.subject.mesh: Adolescent
Antineoplastic Combined Chemotherapy Protocols
Burkitt Lymphoma
Chromosome Aberrations
Comparative Genomic Hybridization
High-Throughput Nucleotide Sequencing
Kaplan-Meier Estimate
Middle Aged
Treatment Outcome
Young Adult
Issue Date: 16-Nov-2015
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.
metadata.dc.identifier.doi: 10.1111/bjh.13849
Appears in Collections:Producción 2020

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