| Background and PurposeDiffuse large B-cell lymphoma(DLBCL)is the most common type of non-Hodgkin’s lymphoma,and its incidence has gradually increased in China in recent years.R-CHOP is currently the standard first-line treatment option,with only 60-70% of patients receiving clinical cure(over 5 years of survival),and about one-third of patients with DLBCL using the standard R-CHOP regimen are not effective.There are several reasons for the prognosis of patients with diffuse large B-cell lymphoma,such as age,high risk of IPI,origin of non-GCB,and advanced stage.In recent years,the genetic abnormalities and protein overexpression of MYC,Bcl-2 and Bcl-6 in DLBCL have been studied in depth,among which double-hit lymphoma(MYC translocation with Bcl-2 or Bcl-6 translocation)And Triple-hit lymphoma(MYC translocation with Bcl-2 and Bcl-6 translocation)have been shown to have a very poor prognosis with the R-CHOP regimen.The R-(DA)EPOCH regimen is considered to be an effective treatment for patients with DHL and with fewer side effects.Immunohistochemical identification of MYC protein expression rate ≥ 40% and Bcl-2 protein expression rate ≥ 50 was defined as double-expressor lymphoma(DEL).Although most studies have shown that MYC/Bcl-2 double-expressor lymphoma has a poor prognosis,the results are still controversial.And in most of these studies,double-expressor lymphomas contain a subset of patients with double-hit lymphoma,as well as patients with MYC,Bcl-2 and Bcl-6 gene breaks and rearrangements,all of which affect the prognosis of patients with double-expressor lymphoma.At present,the therapeutic value of R-(DA)EPOCH regimen for DEL patients remains controversial.Therefore,we excluded all patients with MYC,Bcl-2,and Bcl-6 gene abnormalities by FISH,and studied the prognosis of patients with double-expressor lymphoma and non-double expressor lymphoma in these patients,as well as the efficacy and safety of R-(DA)EPOCH regimen compared with the R-CHOP regimen in patients with DEL.Materials and MethodsA total of 212 patients with diffuse large B-cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from April 1,2015 to October 1,2018 were enrolled,excluding all patients without clear case biopsy,as well as patients with primary central lymphoma and patients with HIV infection.All patients underwent immunohistochemical examination of MYC and Bcl-2.Among them,124 patients underwent MYC and Bcl-2 FISH.After removing double-hit and triple-hit lymphoma patients,119 eligible patients were screened,of which 59 were double expressor lymphoma and 60 were non-double expressor patients.Retrospective study of the incidence of double expressor DLBCL patients and clinical characteristics and survival analysis of patients with MYC/Bcl-2 double expression,and the short-term and long-term effects as well as security analysis of R-(DA)EPOCH regimen and R-CHOP regimen in patients with DEL.Statistical methodStatistical analysis was performed using SPSS21.0 software.Age was analyzed by independent sample t-test,and the remaining clinical and laboratory data Clinical and laboratory data as well as short-term efficacy and adverse effects of R-CHOP and R-(DA)EPOCH groups were compared by chi-square test and Mann Whitney U test.The survival rate of the patients was analyzed by Kaplan-Meier method,and the survival difference between the groups was analyzed by Log-rank method.If the bilateral P value is <0.05,the difference is considered statistically significant.Results1.A total of 212 patients with newly diagnosed diffuse large B-cell lymphoma were enrolled,including 88 patients with MYC/Bcl-2 double expression and 124 patients with MYC/Bcl-2 non-double expression.The incidence of double expression was 41.5%.A total of 124 patients in all patients underwent FISH,and 2 patients with MYC/Bcl-2 and MYC/Bcl-6 double-hit were detected,and all 4 patients were present in the double expression group.To 1 patient with MYC/Bcl-2/Bcl-6 triple-hit lymphoma,this patient was also a double expressor patient with MYC/Bcl-2.Only one patient with MYC/Bcl-2/Bcl-6 triple-hit was detected,and this patient was also a patient with MYC/Bcl-2 double expression.2.Eighty patients with MYC/Bcl-2 double expression were compared with 124 patients with non-double expression.The DEL group was worse than the non-DEL group in both PFS(P=0.030)and OS(P=0.035).3.Among the 124 patients who underwent FISH,the clinical and biological characteristics of 119 eligible patients were summarized after excluding patients with MYC,Bcl-2,and Bcl-6 double and triple hit.Of the 119 patients,76 patients had high MYC expression and 87 had high expression of Bcl-2.59 patients were identified as MYC and Bcl-2 double-expressing lymphoma(DEL),of which 13 patients were of GCB,46 patients were non-GCB,and patients with double-expressing lymphoma were more likely to be non-GCB(P=0.034).Compared with the non-DEL group(N=60),the DEL group(N=59)showed a significant decrease in OS(P=0.048),while the PFS(P=0.456)of the two groups showed a decreasing trend,but no significant statistical difference was observed.4.53 patients with eligible DEL patients were treated with R-(DA)EPOCH regimen and R-CHOP regimen.Of these,33 were treated with R-CHOP and the remaining 20 were treated with R-(DA)EPOCH.The short-term efficacy evaluation showed that in the R-CHOP group,25 patients(75.8%)achieved CR or CRu,1 patient(3.0%)achieved PR,1 patient(3.0%)was SD,and 6 patients(18.2%)achieved PD.Fifteen patients(75.0%)and 2 patients(10.0%)in the R-(DA)EPOCH group achieved CR/CRu and PR,respectively.Two patients(10.0%)developed disease progression after R-(DA)EPOCH treatment.Although the ORR(85.0%)of the R-(DA)EPOCH group did not show a statistically significant difference(P=0.843)compared with the R-CHOP group(78.8%),the efficacy of the R-(DA)EPOCH group was Increased trend.5.Comparison of long-term efficacy of 20 patients with R-(DA)EPOCH regimen and 33 patients with R-CHOP regimen.There were no significant differences between the two groups in either 1-year OS(89.4% vs 88.8%,P=1.000)or 1-year PFS(77.8% vs 73.7%,P=0.508).However,the 2-year PFS(77.8% vs 28.7%,P=0.000)and 2-year OS(80.5% vs 38.1%,P=0.000)were significantly better in the R-(DA)EPOCH group than in the R-CHOP group.And with the prolonged follow-up time,the therapeutic advantages of the R-(DA)EPOCH group were more prominent.6.The hematological and non-hematologic toxicity of the two treatment groups were observed.The incidence of grade 3-4 leukopenia(P=0.000)and grade 3-4 thrombocytopenia(P=0.000)and grade 3-4 anemia(P=0.006)in R-(DA)EPOCH group was significantly higher than that in R-CHOP group,and the residual adverse reactions were mild and there was no significant difference between the two groups.All patients completed the chemotherapy successfully after symptomatic treatment.ConclusionIn diffuse large B-cell lymphoma,patients with MYC/Bcl-2 double expression have a poor prognosis,and the intensive treatment regimen R-(DA)EPOCH is expected to prolong the survival of patients with DEL. |
PDF Full Text Request