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 Blood, 15 September 2008, Vol. 112, No. 6, pp. 2248-2260.
Prepublished online as a Blood First Edition Paper on July 8, 2008; DOI 10.1182/blood-2008-03-145128.

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Submitted March 24, 2008
Accepted June 5, 2008

A prospective clinicopathological 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, and Andrew S. Jack

Medical Oncology Unit, Southampton General Hospital, Southampton, United Kingdom
HMDS, Leeds General Infirmary, Leeds, United Kingdom
Cancer Group, MRC Clinical Trials Unit, London, United Kingdom
Lymphoproliferative Diseases Dept, MSCM Cancer Center, Warsaw, Poland
CR-UK Department of Medical Oncology, Christie Hospital, Manchester, United Kingdom
Peter MacCallum Cancer Centre, East Melbourne, Australia

* Corresponding author; email: wendi.qian{at}ctu.mrc.ac.uk.

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 a MKI67 fraction approaching 100%. Immunophenotype and fluorescent in-situ hybridisation (FISH) were used to separate BL from other aggressive B cell lymphomas. BL was characterised by the presence of a cMYC rearrangement as a sole cytogenetic abnormality occurring in patients with a germinal centre 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 diffuse large B cell lymphoma (DLBCL). 110 clinically fit patients received dm CODOX-M±IVAC (methotrexate dose 3g/m2) according to risk group. 2-year progression-free survival was 64% (95%CI 51%-77%) for BL, 55% (42%-66%) for DLBCL, 85% (73%-97%) for low risk and 49% (37%-61%) for high risk patients. The observed differences in outcome and other clinical features validate the proposed diagnostic criteria. Compared to the previous trial LY06 with full dose (6.7g/m2) methotrexate there was a reduction in toxicity with comparable outcomes. This study was registered at www.clinicaltrials.gov as NCT00040690.


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