Defining Burkitt'S Lymphoma (Bl) With Cytogenetics: Ly10, A Prospective Clinicopathological Study Of Dose-Reduced (Dr) Codox-M/Ivac In Patients With 100% Ki-67 Staining B-Cell Non-Hodgkin'S Lymphoma (Nhl).

7557 Background: Previous studies suggest that CODOX-M/IVAC is effective therapy for BL (Ann Onc 2002 13:1264–74), however the diagnosis of BL in this and other studies was not based on modern immunochemistry and cytogenetics and is unreliable. To re-evaluate this question we prospectively studied a population of patients (pts) with aggressive B-cell lymphoma (100% Ki-67+) uniformly treated with dr CODOX-M/IVAC. Methods: Pts ≤65 years with B-cell lymphomas showing 100% Ki-67, considered fit for chemotherapy, received either dr CODOX-M x 3 or dr CODOX-M/IVAC x 4 according to a modified international prognostic index (IPI). Chemotherapy was modified by methotrexate dose reduction to 3g/m2. Pts >65 years had further dose reductions; unfit pts were studied pathologically only. Tumours were characterised using both an extended panel of antibodies and interphase FISH on paraffin sections for the presence of the C-MYC and BCL-2 rearrangements. Results: Of 126 pts reviewed centrally, 5 were ineligible; 53 were diagnosed as BL, each based on the combination of the presence of re-arrangement of C-MYC as a sole abnormality, germinal centre phenotype and p53 abnormality. The final 68 cases were highly heterogenous with respect to tumour phenotype and cytogenetics and were diagnosed as diffuse large B-cell lymphoma (DLBCL). Median age (all pts) was 44 years (range 17–83), with 23 aged >65. Compared with the DLBCL pts, BL pts were significantly younger (mean 38yrs vs 53 yrs, p < 0.001), had more marrow involvement (45% vs 24%, p = 0.02) and male predominance (83% vs 65%, p = 0.03). Of 104 pts entered into the clincal study, 32 pts (10 BL, 22 DLBCL, IPI 0,1) received dr CODOX-M x 3 and 72 (39 BL, 33 DLBCL, IPI >1) received dr CODOX-M/IVAC x 4. With median follow-up of 15 months (range 1 to 37), 1 year progression-free survival was 58%, 95% CI 48%-68% (54% BL vs 62% DLBCL) and 1 year survival 61% 95% CI 51%-71% (55% BL vs 66% DLBC). Conclusions: The study shows Ki67 is not an accurate approach to the diagnosis of BL and the use of immunocytochemistry and FISH is essential. BL and DLBCL as defined differ markedly clinically. Preliminary data suggest that dr CODOX-M/IVAC has similar activity in both histologies. No significant financial relationships to disclose.