| Background and objectiveDiffuse large B-cell lymphoma(DLBCL)is a highly heterogeneous invasive disease that accounts for 30%-40% of non-Hodgkin’s lymphoma.Double-hit lymphoma(DHL)is an independent subtype defined by 2016 WHO classification of the lymphatic hematopoietic system,which harbored high disease invasiveness and poor prognosis.Some patients have increased gene copy number with MYC,BCL2,BCL6.Double-copy DLBCL has not been clearly defined,but our clinical observations showed that the prognosis of these patients is relatively poor.R-CHOP is the standard first-line regimen for DLBCL,and researchers are constantly exploring the efficacy and safety of R-DA-EPOCH or other stronger programs.There are few studies comparing the prognosis of DHL and double-copy DLBCL at present,and there is no consensus on standard treatment for these two disease subtypes.In this study,we used fluorescence in situ hybridization(FISH)to detect abnormalities of MYC,BCL2 and BCL6 genes,analyzed the prognosis of DHL and double-copy DLBCL,and compared the efficacy of R-DA-EPOCH and R-CHOP regimen in these two disease subtypes.Materials and Methods1.A total of 474 cases of de novo DLBCL diagnosed by histopathology from January 2015 to June 2018 in the First Affiliated Hospital of Zhengzhou University were collected.All patients did not receive any anti-tumor treatment before treatment.The abnormalities of MYC,BCL2 and BCL6 genes were detected by FISH,and there were 127 patients meet the definitions of DHL and double-copy DLBCL.2.127 patients were treated R-CHOP and R-DA-EPOCH regimens,and using log-rank test to analyze the efficacy between two different regimens in DHL and double-copy DLBCL patients.3.Retrospective analysis the following characteristics in 127 patients with DHL and double-copy DLBCL: gender,Ann Arbor staging,IPI score,age,extranodal lymphnode involvement,serum LDH level,presence of large mass,ECOG score,treatment regimens,disease subtypes.To investigate the effects of these factors on the prognosis in DLBCL patients,and to compare the prognostic differences between patients with DHL and double-copy DLBCL.Statistical MethodsAll data were analyzed using SPSS 22.0.The chi-square tests were used to compare categorical variables.Univariate analysis using the Kaplan-Meier method,and the survival rate between two groups was compared by a log-rank test.Prognostic factors were analyzed using COX proportional hazards regression model.All P-values were two-sided with a significance level of 0.05.Results1.The incidence of DHL and double-copy DLBCL: In 474 patients,the incidence of DHL was 5.48%(26/474),and the incidence of double-copy DLBCL was 21.3%(101/474).In 127 patients with FISH positive,26(26/127,20.5%)cases of DHL and 101(101/127,79.5%)cases of double-copy DLBCL,and of which 71(55.9%)were treated with R-CHOP and 56(44.1%)used R-DA-EPOCH regimen.2.Short-term efficacy: The ORR of the R-DA-EPOCH group was higher than that of the R-CHOP group(85.7% vs.63.4%,P =0.005).3.Long-term efficacy: Until the end of follow-up,the median follow-up time was 12 months(range: 1-33 months).In the two schemes,the 2-year PFS and OS was higher for R-DA-EPOCH group than for R-CHOP(PFS: 79.8% vs.57.5%,P =0.002;OS: 81.6% vs.58.5%,P =0.002).Subgroup analysis showed that in 26 patients with DHL,the 2-years survival outcome of the R-DA-EPOCH group was better than that of R-CHOP(PFS: 73.0% vs.28.1%,P =0.001;OS: 68.4% vs.38.2%,P =0.047).In 101 cases of double-copy DLBCL patients,there was also a statistically significant difference between the two treatment regimens(PFS: 82.8% vs.63.2%,P =0.007;OS: 85.3% vs.65.0%,P =0.010),suggesting that either in the DHL or double-copy DLBCL,R-DA-EPOCH regimen was superior to the R-CHOP.The incidence of adverse reactions was similar between R-DA-EPOCH and R-CHOP(P >0.05).4.Prognostic differences between patients with DHL and double-copy DLBCL: For the two disease types,the 2-year PFS in DHL was worse than that of double-copy DLBCL(52.9% vs.72.4%,P =0.008),while no statistical difference was observed in OS(52.9% vs.75.2%,P =0.050).Subgroup analysis showed that the PFS for double-copy DLBCL with MYC and BCL2 was superior to that for DHL with MYC and BCL2(MB2)(73.3% vs.48.2%,P =0.043),this trend is also seen in double-copy DLBCL and DHL with MYC and BCL6(MB6)(73.2% vs.51.4%,P =0.036).5.Analysis of prognostic factors: Multivariate analysis showed that treatment regimens and disease subtypes were independent prognostic factors for FISH positive DLBCL patients(P <0.05).ConclusionIn DHL and double-copy DLBCL,DHL had a worse prognosis than double-copy DLBCL.R-DA-EPOCH was superior to R-CHOP and which was well tolerated.Treatment regimens and disease subtypes may be independent prognosis factors. |
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