To Investigate The Prognosis In Diffuse Large B-cell Lymphoma And Etiology Of Non-Hodgkin Lymphoma

Part one, Prognostic Significance of MYC, MYC/BCL2, p53, and MYC/p53 Expression in Patients with Diffuse Large B-cell LymphomaPurpose:To evaluate the prognostic significance of the expression of MYC, MYC/BCL2, p53, and MYC/p53 in DLBCL.Methods:We included 223 de novo DLBCLs treated with R-CHOP or CHOP in the First Affiliated Hospital of Zhejiang University School of Medicine from March 2009 to April 2015. The expression of MYC and p53 proteins was tested on the formalin-fixed paraffin-embedded tissue specimens by immunohistochemistry technique. The BCL2 expression of all the samples was made up. Subgroups according to patient clinical and immunohistochemical features by the expression of the biomarkers were compared using X2-test and, if necessary, Fisher’s exact test. The prognostic significance of MYC、MYC/BCL2、p53, and MYC/p53 were analyzed by Kaplan-Meier method.In univariate survival analysis, log-rank tests were performed. In multivariate survival analysis, COX Proportional Hazard Model was used.Results:a) Univariate analysis showed that inferior OS and EFS were detected in the patients with MYC+, MYC+/BCL2+, p53+, or MYC+/p53+.b) Multivariate analysis suggested that MYC+, MYC+/BCL2+, p53+, or MYC+/p53+ remained an unfavorable factor of OS as well as EFS, adjusted for the International Prognostic Index stratification, cell of origin and therapy.Conclusions:MYC+, MYC+/BCL2+, p53+, and MYC+/p53+ are all independent risk factors of OS and EFS in DLBCL.Part two, Prognostic Significance of MYC, MYC/BCL2, p53, and MYC/p53 Expression in Patients with Diffuse Large B-cell Lymphoma Treated with Rituximab plus Cyclophosphamide, Doxorubicin, Vincristine, and PrednisonePurpose:To evaluate the prognostic significance of the expression of MYC, MYC/BCL2, p53, and MYC/p53 in DLBCL treated with R-CHOPMethods:We included 148 de novo DLBCLs treated with R-CHOP from the patients enrolled in the first part. MYC and p53 proteins were tested using immunohistochemistry technique. The results were analyzed statistically for the prognostic significance of MYC, MYC/BCL2, p53, and MYC/p53 in DLBCL treated with R-CHOP.Results:a) Univariate analysis showed that MYC+, MYC+/BCL2+, p53+, and MYC+/p53+ confered decreased OS and EFS.b) Multivariate analysis suggested that MYC+, MYC+/BCL2+, and MYC+/p53+ predicted shorter OS as well as EFS, adjusted for the International Prognostic Index stratification and cell of origin.Conclusions:MYC+, MYC+/BCL2+, and MYC+/p53+ are all independent risk factors of OS and EFS for patients with DLBCL under R-CHOP treatment. Therefore, R-CHOP is not the best therapy for these patients and new drugs are requird developing.Part three, HIF-1α Predicts Survival in Patients with Diffuse Large B-Cell LymphomaPurpose:To evaluate the prognostic significance of the expression of HIF-la in DLBCL treated with R-CHOP or CHOP.Methods:We included 155 de novo DLBCLs enrolled in the first part between March 2009 and May 2014 treated with R-CHOP or CHOP. The expression of HIF-la protein was tested by immunohistochemistry technique. HIF-la expression between groups was compared using x-square and, if necessary, Fisher’s exact test. EFS and OS were estimated by Kaplan-Meier method. In univariate analysis, log-rank tests were performed. In multivariate analysis, COX Proportional Hazard Model was used.Results:a) The patients with HIF-1α carried higher BCL6 expression and lower p53 mutation than those with HIF-1α".b) Univariate analysis showed that HIF-1α+ confered longer OS and EFS for the patients treated with R-CHOP.c) Multivariate analysis suggested that HIF-1α+ was an independent predictor of improved OS and EFS for the R-CHOP-treated patients, adjusted for the International Prognostic Index stratification and cell of origin.Conclusions:HIF-1α+ is an independent favorable factor of OS and EFS for patients with DLBCL treated with R-CHOP.Part four, the Risk of Non-Hodgkin Lymphoma in Patients with Systemic Lupus Erythematosus:a Meta-analysisPurpose:To ascertain the correlation between systemic lupus erythematosus (SLE) and the incidence of non-Hodgkin lymphoma (NHL) more comprehensively and precisely by a meta-analysisMethods:Pubmed, the Cochrane Library and Embase databases through June 2014 were searched to identify observational studies evaluating the association between SLE and NHL. The outcomes from these studies were measured as relative risks (RRs). A random or fixed effects model was chosen to calculate the pooled RR according to heterogeneity test. Between-study heterogeneity was assessed by estimating I2 index. Publication bias was assessed by Egger’s test.Results:A total of 12 papers, including 58,098 SLE patients, were suitable for the meta-analysis. The pooled RR was 5.40 (95% CI,3.75-7.77). All the studies produced substantial heterogeneity (I2=74.3%). Subgroup analyses showed that the pooled RRs were 15.37(95% CI,2.90-37.68) for the Asian SLE patients,7.86 (95% CI,4.52-13.70) for the North American SLE patients and 6.74 (95% CI,2.98-15.25) for the European SLE patients. Female SLEs had a lower risk to develop NHL than male SLEs (RR,4.1 vs.9.4). RRs by different age groups were 12.8 for 0-39 y,8.1 for 40-59 y,3.7 for> 60 y-Conclusions:Our data demonstrated an increased risk for NHL in patients with SLE compared with the general population.