Vol 17, No 5 (2015)

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.

Extramedullary lesions in multiple myeloma occur on the extension of neoplastic plasma cells outside the cortical bone. On the local tumor growth the extramedullary mass are found most commonly in vertebrae, ribs, sternum and skull. Single or multiple malignant mass can be found in the skin, liver, breast, kidney and lymph nodes via hematogenous spread of the malignant plasma cells. Incidence of extramedullary lesions in multiple myeloma patients is 7 to 18% at MM diagnosis and up from 2.3 to 20% at relapse or progression. In the last decade, we noted the increase of extramedullary lesions diagnosis at the beginning of the disease that was associated with the wide use of modern x-ray diagnostic methods. Thus, in 2009 the International Myeloma Working Group (IMWG) recommended undergoing the magnetic resonance imaging scans of the spine and pelvis, especially in the absence of osteolytic lesions according to the results of x-ray study. The results of computer tomography allow more accurately find the localization and the sizes of extramedullary mass. Nowadays, it is widely discussed the advantages of positron emission tomography using not only at the beginning of the disease, but also during the treatment, assessing anti-tumour response. The application of standard therapy in case of extramedullary plasmocytomas at the beginning of MM is associated with the reduction of both overall and progression-free survival. Several articles indicate the high efficiency of the programs including bortezomib, there are also some reports concerning the successful application of lenalidomide and pomalidomide in the treatment of MM associated with presence of extramedullary plasmocytomas.