The Clinical Features And Prognostic Analysis Of Patients With Diffuse Large B-cell Lymphoma(DLBCL)

ObjectiveHepatitis B virus (HBV) infection in Non-Hodgkin's lymphoma patients is a common complication. HBsAg-positive NHL patients had an earlier disease onset and more advanced stage. Other studies revealed that HBsAg-positive does not significant impact on the clinical characteristics and prognosis of NHL. Chemotherapy can induce HBV reactivation in Non-Hodgkin's lymphoma patients who are HBsAg-positive, and caused the serious complication of deterioration of hepatic function. Diffuse large B cell lymphoma (DLBCL), as the most common subtype accounted for about 30%~40% of Non-Hodgkin Lymphoma(NHL), and only 30%~40% patients can be cured with CHOP-like regimen. The International Prognosis index (IPI) remains one of the most important prognostic factor for survival with chemotherapy only. DLBCL can be divided into prognostically significant subgroups of germinal centre B-cell-like (GCB) and non-germinal centre B-cell-like (non-GCB) using gene expression profiles microarray techniques or immunohistochemical expression of proteins.This study retrospectively analyzed the outcomes and the clinical prognostic factors in DLBCL patients, who are treated with CHOP-like regimen at first-line or given salvage treatment at relapse or refractory diseases. At the same time, research was did to clinical and survival characteristic in HBV carriers with DLBCL.Methods155 DLBCL patients who had confirmed by histological pathology diagnosis and treatment in the Cancer Hospital of Shantou University Medical College from December 1996 to December 2008 were retrospectively analyzed, in which male 86 cases and female 69 cases.125 patients with data integrity was then be analyzed. The type of lymphoma was diagnosed according to the World Health Organization(WHO) classification criteria, confirmed with immunohistochemistry method, by Ann Arbor staging; 125 patient were treated with CHOP-like regimen at first-line, while salvage regimen such as ICE,MVp-16 and EPOCH was given to 40 relapse or refractory patients. Then response was evaluated according to Cheson standardize response criteria. Clinical characteristic, remission rate, survival rate, and the comparison of clinical features and response relative factors between HBsAg-positive and negative group were studied. The overall survival was calculated from the date of diagnosis to the data of death or the last follow-up.SPSS for windows V. 17.0 was used to statistical analysis. Kaplan-Meier was applied to assess the survival probability, and the differences between two groups were compared by log-rank test. The multivariate analysis of outcome in terms of OS was performed by Cox regression which included the variables that were significant in univariate analysis. Statistical diffetences in the clinical parameters and treatment characteristic between HBsAg-positive and HBsAg-negative groups were evaluated by either Chi-square test or Fish's exact test for categorical parameters, andμtest for continunous variables. A two-tailed p value of less than 0.05 was considered statistically significant.Results1 Clinical features and outcome of DLBCL in our hospitalTotal of 125 patients in this study. The ratio of males to females was approximately 1.3:1. The median age of patients was 49 years. The Ann Arbor classification showed that 52.0% of cases were of stageⅢandⅣ. 42.1% of cases had elevated serum lactate dehydrogenase(LDH). 22.6% of patients were in a median & high-risk groups of IPI score. The superficial lymph nodes as first symptom took 60.0%, 72.8% appeared extranodal involvement. The median number of chemotherapy cycle was 5, 38.4% achieved CR and 44.8% achieved PR, With median followed-up was 28.2 months, median overall survival was 46.5months, The 3-year OS and 5-year OS rates were 51.9% and 48.9%,respectively. In univariate analysis show that age≤60 years old, Ann Arbor stageⅠ~Ⅱ, normal LDH level, good performance status(ECOG 0~1), lower IPI scores, without marrow or liver involvement, combined with radiotherapy, without B symptom and remission were statistically significant favourable prognostic factor. In multivariate analysis only the high IPI scores (P=0.000) , without radiotherapy (P=0.045) and not remission(P=0.049) were statistically significant unfavourable independent prognostic factors for DLBCL patients. Risk of death increased 1.055 times with each one IPI score, and reduced 1.600 time with radiotherapy, was 1.597 times higher in patients could not gain remission.2 Treatment outcomes and prognostic analyses DLBCL with salvage chemotherapyAll of the 40 patients received conventional salvage regimen, with the remission rate 60.0% (24/40). By the end of Feb.2010, the median follow-up time was 15.5 (1.2~59.8) months, 8 patients still alive. The median survival time after relapse was 11.2 (0.8~59.8) months. The 1-, 2-, and 3-year overall survival rates were 42.7%, 23.8% and15.9%, respectively. The median overall survival was 12.2 months for low-median risk group (IPI: 0~2 score) and 4.1 months for median-high risk group (IPI: >2), respectively (P<0.001).Multivariate analysis showed that only IPI score was independent prognostic factors of relapsed or refractory DLBCL.3 The clinical features of Hepatitis B virus carriers with diffuse large B cell lymphomaThere were 41(34.17%)HBsAg-positive patients versus 79(65.83%)negative ones;The median age in HBsAg-positive group was 43 while HBsAg-negative group 55 (P=0.009). Compared with the negative group, the hepatic dysfunction rate caused by chemotherapy was 34.15% vs. 25.32% (P>0.05). The median survival time (MST) was 68.5months in this study, and 3-year overall survival rate reached to 55.20%; HBsAg-positive group showed 29.80months of MST and 3-year overall survival rate 44.70%, while MST did not reach and 3-year overall survival rate was 61.00% in the HBsAg-negative group (χ2=1.291, P=0.265). In the HBsAg-positive group, hepatic dysfunction has no influence on survival.Conclusions1 The media age of diagnosis is 49 in DLBCL patients in our hospital, with the superficial lymph node as the main first symptom, with high extranodal involvement rate, advanced stage, low-risk, nearly 1/2 accompanied with LDH increase. 2 The remission rate was high, and MST was 46.5, approximate to half patients could survive to 5 years.3 Unfavourable independent prognosis factors for DLBCL were high IPI scores, without radiotherapy and not remission.4 The patients received conventional salvage regimen reached response rate 60.0%, MST 11.2months, 3-ys OS 15.9%.5 The median-high IPI score may be unfavourable independent prognostic factors for relapse/refractory patients6 Hepatitis B virus carriers had an earlier onset for DLBCL; No significant difference was found between the two groups in their clinical characteristics, remission rate, median survival time, overall survival rate and chemotherapy related hepatic function damage.