Abstract
The introduction of rituximab, a chimeric monoclonal antibody against the CD20 antigen has significantly improved the treatment outcome of diffuse large B-cell lymphoma (DLBCL). However, not all patients with DLBCL respond to rituximab plus CHOP (R-CHOP) chemotherapy. Thus, resistant clones of DLBCL remain a significant clinical problem. Although the underlying mechanisms of this resistance are still not clear, considering that the dysregulation of the balance between cell survival and programmed cell death is a central feature of lymphomagenesis, a factor promoting survival of lymphoma cells may be associated with resistance of DLBCL to rituximab. B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily has shown to be a key mediator in the formation and regulation of normal B-cell response. BAFF is usually expressed by monocytes and macropahges, and is promoting cell survival and preventing apoptosis. Therefore, we performed this study to determine the clinical impact of serum BAFF on the treatment outcome of DLBCL treated with R-CHOP. 48 patients diagnosed as DLBCL were enrolled, and all the patients were treated with R-CHOP every 3 weeks. Before treatment and every two cycles of R-CHOP, their serum was taken and cryopreserved. The level of BAFF was measured by ELSA method (Human BAFF immunoassay, R&D systems, USA). We also analyzed the expression of BAFF receptor in tumor sections by immunohistochemistry (Polyclonal antibody to BAFF receptor, Abcam, UK). Median age of the patients was 56 years old (range 21–79). 20 patients were stage I/II, and 28 were stage III/IV. Rituximab was administered at the dosage of 375mg/m2 on day1, and CHOP chemotherapy was combined with rituximab until 6 – 8 cycles. The mean level of BAFF at the time of diagnosis was 2284.54pg/mL, and the median was 1326.60pg/mL (138.80–13537.92pg/mL). When the patients were dichotomized into high and low BAFF group based on the median value, 21 patients showed complete response in low BAFF group, however, only 3 patients showed complete response in high BAFF group (p=0.011). Among 16 patients showing relapse, 11 patients belonged to high BAFF group. The expression of BAFF receptor was also increased in relapsed patients compared to non-relapse group (p < 0.05). In the analysis of relapse-free survival, low BAFF group did not reach the median value as yet while high BAFF group showed 379 days (p=0.046). Thus, baseline serum BAFF may be associated with response of DLBCL to R-CHOP. When we serially checked the level of serum BAFF, the level of BAFF was increased during treatment (After the 2nd cycle 6448.56pg/mL, and after 4th cycle 7421.28pg/mL). In conclusion, serum B-cell activating factor may be a useful indicator predicting response to R-CHOP and prognosis in patients with DLBCL.
Figure Figure
MicroRNAs regulate key cell survival pathways and mediate chemosensitivity during progression of diffuse large B-cell lymphoma