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<p>Abstract</p> <p>Background</p> <p>The precise mechanism of action for rituximab (R) is not fully elucidated. Besides antibody-dependent cellular cytotoxicity (ADCC), complements may also play an important role in the clinical response to rituximab-based therapy in diffuse large B cell lymphoma (DLBCL). The purpose of this study was to explore the relationship between <it>C1qA</it>_{<it>[276]</it>} polymorphism and the clinical response to standard frontline treatment with R-CHOP in DLBCL patients.</p> <p>Methods</p> <p>Genotyping for <it>C1qA</it>_{<it>[276A/G]</it>} was done in 164 patients with DLBCL. 129 patients treated with R-CHOP as frontline therapy (R ≥ 4 cycles) were assessable for the efficacy.</p> <p>Results</p> <p>Patients with homozygous A were found to have a higher overall response rate than those with heterozygous or homozygous G alleles (97.3% vs. 83.7%,<it>P</it> = 0.068). The complete response rate in patients with homozygous A was statistically higher than that in AG and GG allele carriers (89.2% vs. 51.1%,<it>P</it> = 0.0001). The overall survival of patients with homozygous A was longer than that of the G allele carriers (676 days vs. 497 days, <it>P</it> = 0.023). Multivariate Cox regression analysis showed that <it>C1qA</it> A/A allele was an independent favorable prognostic factor for DLBCL patients treated with R-CHOP as first-line therapy.</p> <p>Conclusion</p> <p>These results suggest that <it>C1qA</it> polymorphism may be a biomarker to predict response to R-CHOP as frontline therapy for DLBCL patients.</p>