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)

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. (Blood.

Treatment Outcome of Adult Burkitt Lymphoma in Japanese Patients with Modified LMB Protocol : A Single Center Retrospective Analysis

“…This development appears to have improved the prognosis of adult BL. [3][4][5]8,10,14,15 The effectiveness of LMB protocol for adult BL was reported in 1995, 10 which was one of the earliest reports describing successful treatment of adult BL using HD-MTX. The original CODOX-M/IVAC was also reported by Magrath et al in 1996, 3 although this protocol was modified through clinical studies; 4,5 the reduction of MTX was among major changes because the principal cause of toxicity in the original CODOX-M/IVAC was the use of MTX at 6.7 g/m 2 in a single course.…”

“…1,2 Despite its highly aggressive course, the prognosis of BL has improved after the introduction of rapidly cycling, intensive chemotherapy regimens such as the "LMB (Lymphoma Malignancy B) protocol" (originally reported by a French group) and "CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin, methotrexate/ifosfamide, etoposide, and cytrabine) therapy" that include high-dose methotrexate (HD-MTX). [3][4][5] However, most of the studies testing these regimens were performed in European and North American populations and their suitability for other populations remains to be determined.…”

The role of hematopoietic SCT in adult Burkitt lymphoma

“…Indeed, in the LY10 study that was conducted by the United Kingdom Medical Research Council (MRC) and the National Cancer Research Institute (NCRI) Lymphoma Clinical Studies Group, OS was 88% in the group defined as low risk, whereas it was only 52% in the high-risk group, with a PFS of 49% in the latter. 19 Although it would be advisable to identify high-risk patients at presentation and for them to be discussed in the context of a transplant multidisciplinary meeting, there is no consensus as to how to identify this subset of patients. A number of high-risk parameters have been identified in studies and trials have varied in how they risk stratify patients (Tables 1 and 2).…”

“…21 However, up to 90% and 80% of patients may have an elevated serum LDH and stage III-IV disease, respectively, and stratifying on the basis of these parameters may not allow sufficient discrimination between subsets of patients. 9,14,19,22,23 A recent Swedish population-based study derived a score based on age 440 years, performance status 41 and serum LDH 4upper limit of normal to be significant in predicting survival in multivariate analysis of 156 adult patients with BL treated between 2000 and 2010. Although such a score may serve as a useful tool in risk stratifying patients who have been treated with current regimes, further validation would be desirable, especially in the context of patients undergoing SCT.…”

Stage IV adult sporadic Burkitt lymphoma/leukemia with complex bone marrow cytogenetics is associated with a very poor outcome

“…All patients were HIV-negative and received treatment with alternating CODOX-M/ IVAC as per LY06 or LY10, with or without RTX. 4,6 The median age was 42 years (range, 19-69 years). Patients were diagnosed by a specialist hematopathology service according to WHO criteria.…”