The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose-intensive chemotherapy including rituximab
Por:
Forero-Castro, M, Robledo, C, Lumbreras, E, Benito, R, Hernandez-Sanchez, JM, Hernandez-Sanchez, M, Garcia, JL, Corchete-Sanchez, LA, Tormo, M, Barba, P, Menarguez, J, Ribera, J, Grande, C, Escoda, L, Olivier, C, Carrillo, E, de Coca, AG, Ribera, JM and Hernandez-Rivas, JM
Publicada:
1 feb 2016
Categoría:
Hematology
Resumen:
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=0038), shorter progression-free survival (PFS; P=0007) and overall survival (OS; P=0009). The integrative analysis of array-CGH and NGS showed that 263% (5/19) and 368% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS (P=0011) while TCF3 alterations were associated with shorter OS (P=0032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol.
Filiaciones:
Forero-Castro, M:
Univ Salamanca, CSIC, IBMCC, Canc Res Ctr,IBSAL, E-37008 Salamanca, Spain
Pedag & Technol Univ Colombia UPTC, Sch Biol Sci GEBI MOL, Bogota, Colombia
Robledo, C:
Univ Salamanca, CSIC, IBMCC, Canc Res Ctr,IBSAL, E-37008 Salamanca, Spain
Lumbreras, E:
Univ Salamanca, CSIC, IBMCC, Canc Res Ctr,IBSAL, E-37008 Salamanca, Spain
Benito, R:
Univ Salamanca, CSIC, IBMCC, Canc Res Ctr,IBSAL, E-37008 Salamanca, Spain
Hernandez-Sanchez, JM:
Univ Salamanca, CSIC, IBMCC, Canc Res Ctr,IBSAL, E-37008 Salamanca, Spain
Hernandez-Sanchez, M:
Univ Salamanca, CSIC, IBMCC, Canc Res Ctr,IBSAL, E-37008 Salamanca, Spain
Garcia, JL:
Studies Inst Hlth Sci Castilla & Leon IESCYL, Salamanca, Spain
Corchete-Sanchez, LA:
Univ Hosp Salamanca, Dept Haematol, Salamanca, Spain
Tormo, M:
Clin Univ Hosp Valencia, Dept Haematol, Valencia, Spain
Barba, P:
Vall dHebron Hosp, Dept Haematol, Barcelona, Spain
Menarguez, J:
Gregorio Maranon Hosp, Dept Pathol, Madrid, Spain
:
Jose Carreras Res Inst, ICO, Hosp Germans Trias & Pujol, Dept Clin Haematol, Badalona, Spain
Grande, C:
Univ Hosp October 12, Dept Haematol, Madrid, Spain
Escoda, L:
Univ Hosp Tarragona Joan XXIII, Dept Haematol, Tarragona, Spain
Olivier, C:
Gen Hosp Segovia, Dept Haematol, Segovia, Spain
Carrillo, E:
Univ Hosp Virgen del Rocio, Dept Haematol, Seville, Spain
de Coca, AG:
Clin Univ Hosp Valladolid, Dept Haematol, Valladolid, Spain
:
Jose Carreras Res Inst, ICO, Hosp Germans Trias & Pujol, Dept Clin Haematol, Badalona, Spain
Hernandez-Rivas, JM:
Univ Salamanca, CSIC, IBMCC, Canc Res Ctr,IBSAL, E-37008 Salamanca, Spain
Univ Hosp Salamanca, Dept Haematol, Salamanca, Spain
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