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Br J Haematol. 2016 Feb;172(3):428-38. doi: 10.1111/bjh.13849. Epub 2015 Nov 16.

The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose-intensive chemotherapy including rituximab.

Author information

1
Cancer Research Centre, IBSAL, IBMCC, University of Salamanca, CSIC, Salamanca, Spain.
2
School of Biological Sciences (GEBIMOL), Pedagogical and Technological University of Colombia (UPTC), Colombia, IN, USA.
3
Studies Institute of Health Sciences of Castilla and León (IESCYL), Salamanca, Spain.
4
Haematology Department, University Hospital of Salamanca, Salamanca, Spain.
5
Haematology Department, Clinical University Hospital of Valencia, Valencia, Spain.
6
Haematology Department, Vall d'Hebron Hospital, Barcelona, Spain.
7
Pathology Department, Gregorio Marañón Hospital, Madrid, Spain.
8
Clinical Haematology Department ICO-Hospital Germans Trias i Pujol, Jose Carreras Research Institute, Badalona, Spain.
9
Haematology Department, University Hospital October 12, Madrid, Spain.
10
Haematology Department, University Hospital of Tarragona Joan XXIII, Tarragona, Spain.
11
Haematology Department, General Hospital of Segovia, Segovia, Spain.
12
Haematology Department, University Hospital Virgen del Rocío, Seville, Spain.
13
Haematology Department, Clinical University Hospital of Valladolid, Valladolid, Spain.

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.

KEYWORDS:

Burkitt lymphoma; array-based comparative genomic hybridization (aCGH); next-generation sequencing; outcome; rituximab

PMID:
26567765
DOI:
10.1111/bjh.13849
[Indexed for MEDLINE]

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