Abstract

Background: In previous several studies it was confirmed that double expression of both c-myc and bcl-2 in Diffuse Large B-cell lymphoma patients (DLBCL) predict aggressive course. We suggest that it can be independent risk factor and early treatment intensification can provide potential benefit for this poor risk group. Methods: To analyze data we used chi-square test for independence, odds ratio (OR), full analisys test. Progression free survival (PFS) were estimated by Kaplan-Meier method, comparison of PFS in experimental groups (long-rank test), multifactor analysis of PFS (multinomial logistic regression). Statistically significant difference if p < 0,05. Results: We analyzed 240 pts with DLBCL, from 18 to 85 y.o. (median age 56 y.o), who underwent treatment in National Medical Research center from 2008 to 2018. Seventy six (32%)-with early stage of disease (I,II) and 164 pts (68%)-advance stage (III,IV). Extranodal involvements were observed in 61 pts (25%) and B-symptoms in 109 (45%), GCB-subtype in 47% and non-GCB in 53% (Hans algorithm). DA-EPOCH-R, Hyper-CVAD-R as first line received 26 pts (11%) and up-front high-dose chemotherapy with AutoSCT received 17 pts (7%). 2-years PFS was 86% for all pts [95% CI 78-94]. PFS was significantly lower in pts with B-symptoms (38% vs 84%; RR 3,3 [95% CI 0,85 – 1,4], p < 0,05); advance stage (42% vs 89%; RR 3,0 [95% CI 1,7 – 2,1], p < 0,05); c-myc expression (45% vs 84%); RR 1,9 [95% CI 0,3 - 0,9 ], p < 0,05); bcl-2-expression (60% vs 83%) RR 1,6 [95% CI 1,2 – 1,9], p < 0,05); Ki-67 higher than 70% (59% vs 89%; RR 2,5 [95% CI 0,9 – 1,2], p < 0,05). Double-expressor lymphoma (DEL) (both c-myc and bcl-2) were observed in 33% (80 patients). Among patients with DEL, PFS were lower but not significantly different comparing with non-DEL (p = 0,03). These data were related to early treatment intensification in this subgroup (DA-EPOCH-R, Hyper-CVAD-R, up-front high-dose chemotherapy with AutoSCT). DEL subgroup was also associated with advance stage of the disease (III-IV 68% vs I-II 39%, p < 0,05), B-symptoms (69% vs 47%, p = 0,03) and Ki-67 higher than 70% (81% vs 71%, p > 0,05). Conclusions: These data confirm more aggressive course of the disease in patients with DEL comparing with standard group and may suggest benefit for patients to undergo early-treatment intensification. Legal entity responsible for the study: Tatiana Semiglazova. MD. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

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