Current possibilities in diagnosis and treatment of diffuse large B cell lymphoma in children and adolescents: results of Pediatric Hematology and Oncology Research Institute of N.N.Blokhin Russian Cancer Research Center, international experience

Background/Objectives. At the present time results of some pediatric protocols (FAB/LMB96 with and without rituximab (±R), B-NHL-BFM90/95, B-NHL-2004m) were published but prognostic significance of markers, such as: non-GCB DLBCL subtype, C-MYC, pSTAT3, BCL2/C-MYC coexpression, C-MYC, BCL2/C-MYC gene rearrangements in childhood DLBCL is unknown. In this article there was presented results of treatment childhood DLBCL according to protocols IDM-NHL-BFM90, B-NHL-BFM95 ± rituximab in view of morpho-immunological tumor’s features.Design/Methods. From 1994 to 2015 fifty one pediatric patients with DLBCL were included in trials IDM-NHL-BFM90, B-NHL-BFM95 ± rituximab. Male/female ratio was 2/1. Median age - 9.9±0.5 years (range from 2 till 16). Stage III-IV were revealed in 29 patients (56.9%), R3-R4-risk group - in 26 (50.9%). GCB/non-GCB DLBCL subtypes were assessed by Hans, Tally and Visco-Young immunohistochemical algorithms. Cutoff values of 40% for MYC, 70% for BCL2, 50% for pSTAT3 were established. MYC gene rearrangement was assessed by FISH using locus-specific MYC (8q24) tricolor breakapart probe, MYC (8q24) SE8 control probe and locus-specific MYC, BCL2, BCL6 dual - color breakapart probes.Results. GCB/non-GCB DLBCL subtypes were revealed in 13 (54.2%) and 11 (45.8%) out of 24 cases; in 10 (41.7%)and 14 (58.3%) out of 24 cases according to Hans algorithm, 10 (43.5%) and 13 (56.5%) out of 23 cases according to Visco-Young algorithm; in 7 (63.6%) and 4 (36.4%) out of 11 cases according to Tally algorithm. There was a trend to determine the difference between GCB/non-GCB subgroups of DLBCL according immunohistochemical algorithms (p=0.058). Ten (62.5%) out of 16 DLBCL samples were positive for MYC, 9 (40.9%) out of 22 - for BCL2, 2 (18.2%) out of 11 - for BCL2/C-MYC coexpression, 1 (9.1%) out of 11 - for pSTAT3. MYC gene rearrangement was revealed in 3 (20%) out of 15 patients. There was determined a statistically significant relationship between MYC expression>70% and MYC gene rearrangement in patients with III - IV stages of disease and R3 - R4 risk group. BCL2 and BCL-6 gene rearrangements were not revealed. Five-year overall survival (OS), event-free survival (EFS) were 90.3±5.3%, a median follow-up was 63.3±7.9 months, relapse-free (RFS) was 100%, a median follow-up was 69.5±7.9 months. There is not revealed any influence of investigated markers on OS, EFS and RFS.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.