Abstract

IntroductionThe international prognostic index (IPI) was a most common prognostic score in patients with aggressive non-Hodgkin lymphoma. Therefore, rituximab improved OS in patients with diffuse large B-cell lymphoma (DLBCL), revised IPI (R-IPI) was suggested. Although, the 5-year OS is higher than 50% in patients of high risk R-IPI. National Comprehensive Cancer Network published an enhanced IPI (NCCN-IPI) for improving risk stratification. However, NCCN-IPI didn't enough evaluate clinical and disease characteristics, for example beta-2-microglobulin (B2MG), cell of origin, albumin, soluble interleukin-2 receptor (sIL-2R). Aim of this study is to evaluate clinical and disease prognostic factor in patients with DLBCL.MethodsWe retrospectively analyzed 647 patients who were newly diagnosed de novo DLBCL and treated with R-CHOP in our hospital from January 2005 to December 2016. We excluded primary central nervous system lymphoma and transformed from low grade B-cell lymphoma. Median follow-up time is 58.5 months (range; 2-160 months.).We collected data of blood and imaging test before chemotherapy. The patient's baseline clinical and disease characteristics included age, Ann Arbor stage, serum albumin, bulky, B symptoms (defined as recurrent fever, night sweats, or >10% weight loss), B2MG, cell of origin, cluster of differentiation (CD) 5 positive, serum C-reactive protein (CRP), ECOG performance status (PS), ferritin, gender, lactate dehydrogenase (LDH), sIL-2R, monocyte, number and site of involvement extranodal. We evaluate over 60-years old, advance stage (Ann Arbor stage Ⅲ-Ⅳ) and more than PS 2. We defined the cut-off value of B2MG, CRP, ferritin, sIL-2R, monocyte and albumin by using receiver operating characteristic curves. LDH was over the upper limit of normal. Cell of origin was classified by Hans' algorithm. CD 5 was evaluated by immunohistochemistry. The univariate analyses of between factors and OS was used in univariate of log-rank test. And the multivariate analysis was used cox proportional hazards regression analysis.ResultsThe patient's median age was 65 years old (range 17-90 years old.). The cut-off value of B2MG is ≧2.23 mg/L, CRP is ≧0.4 mg/dl, ferritin is ≦250 ng/ml, sIL2-R is ≧1000 U/mL, monocyte is ≧608 /μL and serum albumin is ≦3.4 g/dl.In the result of univariate analysis, age, stage, albumin, B symptoms, B2MG, CD5, CRP, PS, ferritin, LDH, sIL-2R, monocyte, nonGCB, the number of extranodal sites (>1) and the involvement of bonemarrow, liver, lung, muscle, skin and pancreas affected OS. In multivariate analysis, the worse prognostic factors were age (Hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.27-3.57, p<0.01), albumin (HR 1.59, 95% CI 1.01-2.51, =0.047), B2MG (HR 1.86, 95% CI 1.18-2.93, p<0.01), PS (HR 2.01, 95% CI 1.22-3.33, p<0.01), sIL-2R (HR 1.75, 95% CI 1.11-2.76, p=0.016), pancreas (HR 4.43, 95% CI 1.75-11.22, p<0.01) and skin (HR 1.94, 95% CI 1.11-3.39, p=0.021).Albumin, B2MG and sIL-2R weren't included prognostic score of IPI, R-IPI and NCCN-IPI. In order to validate we developed prognostic score consisting of 5 factors (age, PS, B2MG, sIL-2R and albumin). And compared with NCCN-IPI in our data. We categorized patients into 4 risk groups: low (0 factor), low-intermediate (1 factor), high-intermediate (2 or 3 factors), high (4 or 5 factors). The low risk of 5-year OS was 91.5%, low-intermediate risk was 86.2%, high-intermediate risk was 72.3% and high risk was 37.4%. The low risk of NCCN-IPI was 95.1%, low-intermediate was 86.2%, high-intermediate was 68.8% and high was 50.6%. The absolute difference in the 5-year OS between low and high risk groups was 54.1% with our study prognostic score compared with 44.5% with NCCN-IPI in our study.ConclusionsOur study suggest that B2MG, sIL-2R and serum albumin are significant prognostic factors in patients with DLBCL in the rituximab era. [Display omitted] DisclosuresYokoyama:Chugai pharmaceutical inc, Roche: Other: commissioned work. Mishima:Chugai pharmaceutical inc, Roche: Other: commissioned work. Nishimura:Chugai pharmaceutical inc, Roche: Other: commissioned work. Terui:Novartis pharma: Honoraria; Takeda pharmaceutical: Honoraria; Janssen Pharmaceutical KK: Honoraria; Celgene: Honoraria; Bristol myers Squib: Honoraria.

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