Современная онкология (Dec 2015)
Modern aspects of differential diagnosis and treatment of large B-cell lymphomas with mediastinum involvement in children and adolescents
Abstract
Background. At the present time results of some pediatric protocols (FAB/LMB96 with and without rituximab, B-NHL-BFM90/95, B-NHL-2004m) were published but prognostic and diagnostic significance of markers, such as: C-MYC, STAT3, pSTAT3, TRAF1 expression, C-MYC gene rearrangement and amplification in childhood large B-cell lymphomas with mediastinum involvement is unknown. In this article there were presented results of treatment childhood large B-cell lymphomas with mediastinum involvement according to protocols IDM-NHL-BFM90, B-NHL-BFM 95 ± rituximab in view of morpho-immunological tumor’s features.Design/Methods. From 1994 to 2015 twenty two pediatric patients with large B-cell lymphomas with mediastinum involvement were included in trials IDM-NHL-BFM90, B-NHL-BFM 95 ± rituximab. Male/female ratio was 1/2. Median age - 12.2±0.6 years (range from 5 till 18). Median of age was 13.5 years. Stage III-IV, R3-R4 risk groups were revealed in all patients (100%). GCB/non-GCB DLBCL subtypes were assessed by Hans and Visco-Young immunohistochemical algorithms. Cutoff values of 40% for MYC, 70% for BCL2, 20% for STAT3, 50% for pSTAT3tyr705, TRAF1, TNFAIP2 were established. MYC gene rearrangement and amplification were assessed by FISH using locus-specific MYC (8q24) tricolor breakapart probe and MYC (8q24) SE8 control probe.Results. According to the data of this clinical trial there were revealed distinctive features of molecular portrait childhood primary mediastinal (thymic) large B-cell lymphoma that include: CD20 expression in all patients, high frequency of CD23, CD30, C-MYC, PAX5, TRAF1, TNFAIP2 expression, absence of CD10, pSTAT3tyr705 expression, low frequency of IgM expression, absence of C- MYC gene rearrangement and/or amplification despite the level of C-MYC expression more 70%, high activity of JAK2-JMJD2C epigenetic regulation of pSTAT3tyr705 independent C-MYC expression. There is the tendency to the formation of molecular portrait of childhood diffuse large B-cell lymphoma with mediastinum involvement: CD20 expression in all patients, non-GCB variant, high frequency of C-MYC expression, C-MYC gene rearrangement, absence of CD23, TRAF1, TNFAIP2 expression, low frequency of CD30 expression.Using protocol B-NHL-BFM 95 plus rituximab we have achieved high level of relapse-free survival in patients with large B-cell lymphomas with mediastinum involvement. There is not revealed any influence of investigated markers (CD23, CD30, C-MYC) on overall survival, event-free survival and relapse-free survival.Conclusion. Number of patients in this study is not enough to estimate authentic prognostic significance of these markers but high-intensive B-NHL-BFM95 + rituximab chemotherapy showed good therapeutic effect in our patients. This study will be continued.
