A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial)
Graham M Mead, Sharon L Barrans, Wendi Qian, Jan Walewski, John A Radford, Max Wolf, Simon M Clawson, Sally P Stenning, Claire L Yule, Andrew S Jack, UK National Cancer Research Institute Lymphoma Clinical Studies Group, Australasian Leukaemia and Lymphoma Group, G M Mead, A Jack, S Barrans, W Qian, S Stenning, S Clawson, C Goldstein, C Yule, J Stone, R Glynne-Jones, R Prescott, H Scarffe, Graham M Mead, Sharon L Barrans, Wendi Qian, Jan Walewski, John A Radford, Max Wolf, Simon M Clawson, Sally P Stenning, Claire L Yule, Andrew S Jack, UK National Cancer Research Institute Lymphoma Clinical Studies Group, Australasian Leukaemia and Lymphoma Group, G M Mead, A Jack, S Barrans, W Qian, S Stenning, S Clawson, C Goldstein, C Yule, J Stone, R Glynne-Jones, R Prescott, H Scarffe
Abstract
This prospective study aimed to develop reproducible diagnostic criteria for sporadic Burkitt lymphoma (BL), applicable to routine practice, and to evaluate the efficacy of dose-modified (dm) CODOX-M/IVAC in patients diagnosed using these criteria. The study was open to patients with an aggressive B-cell lymphoma with an MKI67 fraction approaching 100%. Immunophenotype and fluorescent in situ hybridization (FISH) were used to separate BL from other aggressive B-cell lymphomas. BL was characterized by the presence of a cMYC rearrangement as a sole cytogenetic abnormality occurring in patients with a germinal center phenotype with absence of BCL-2 expression and abnormal TP53 expression. A total of 128 patients were eligible for the study, of whom 58 were considered to have BL and 70 to have diffuse large B-cell lymphoma (DLBCL). There were 110 clinically fit patients who received dmCODOX-M (methotrexate, dose 3 g/m(2)) with or without IVAC according to risk group. The 2-year progression-free survival was 64% (95% confidence interval [CI] 51%-77%) for BL, 55% (95% CI 42%-66%) for DLBCL, 85% (95% CI 73%-97%) for low risk, and 49% (95% CI 38%-60%) for high-risk patients. The observed differences in outcome and other clinical features validate the proposed diagnostic criteria. Compared with the previous trial LY06 with full-dose methotrexate (6.7 g/m(2)), there was a reduction in toxicity with comparable outcomes. This study was registered at www.clinicaltrials.gov as NCT00040690.
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Source: PubMed