Minimal Disseminated Disease in High-Risk Burkitt's Lymphoma Identifies Patients With Different Prognosis

Abstract

To study minimal disseminated disease (MDD) in children with Burkitt's lymphoma (BL) and to determine its impact on prognosis. We established a simplified long-distance polymerase chain reaction (LD-PCR) assay that can amplify up to 15 to 20 Kb of DNA sequence, making it possible to detect the t(8;14) at the genomic level with sensitivity of 10(-4). We prospectively studied diagnostic biopsies and bone marrow aspirates from 134 patients affected by BL. A specific LD-PCR product was detected in 96 (72%) of 134 BL biopsies. Among 84 patients with t(8;14) positivity on tumor biopsy and bone marrow (BM), 26 (31%) had LD-PCR-positive BM, and 15 (18%) were positive at standard morphologic analysis. Twenty (85%) of 26 MDD-positive patients belonged to the R4 risk group, according to Berlin-Frankfurt-Munster definition. The 3-year progression-free survival was 68% (SE, 10%) in MDD-positive patients in R4 compared with 93% (SE, 5%) in MDD-negative patients in R4 (P = .03). By multivariate analysis (including MDD, sex, lactate dehydrogenase, CNS involvement), only MDD was predictive of higher risk of failure (hazard ratio, 4.7; P = .04). MDD identifies a poor-prognosis subgroup among children with high-risk BL. To improve disease control in these patients, a more effective risk-adapted therapy, possibly including anti-CD20 monoclonal antibody, should be considered.