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The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose‐intensive chemotherapy including rituximab
Author(s) -
ForeroCastro Maribel,
Robledo Cristina,
Lumbreras Eva,
Benito Rocio,
HernándezSánchez Jesús M.,
HernándezSánchez María,
García Juan L.,
CorcheteSánchez Luis A.,
Tormo Mar,
Barba Pere,
Menárguez Javier,
Ribera Jordi,
Grande Carlos,
Escoda Lourdes,
Olivier Carmen,
Carrillo Estrella,
García de Coca Alfonso,
Ribera JosepMaría,
HernándezRivas Jesús M.
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13849
Subject(s) - rituximab , medicine , lymphoma , oncology , chemotherapy , comparative genomic hybridization , burkitt's lymphoma , biology , gene , genetics , genome
Summary 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 TP 53, TCF 3 (E2A), ID 3 and GNA 13 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 TP 53 and TCF 3 genes, respectively. TP 53 alterations were associated with shorter PFS ( P = 0·011) while TCF 3 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.