Serum Uric Acid Level Is A Prognostic Indicator And Improves The Predictive Ability Of The IPI Score In Diffuse Large B-cell Lymphoma

【Background】Numerous epidemiology studies have shown that high levels of serum uric acid(serum uric acid,SUA)is associate with negative clinical outcome in various malignancies.This study investigates whether SUA,at the time of diagnosis,has a prognostic significance in patients with diffuse large B-cell lymphoma(diffuse large B cell lymphoma,DLBCL).In addition,whether integrating SUA to the IPI score could improve the survival prediction and risk stratification of DLBCL patients.【Methods】 We retrospectively evaluated 167 Chinese patients with newly diagnosed DLBCL under rituximab(R)-CHOP or CHOP-like immune-chemotherapy from January 2008 to July 2016.The optimal cutoff value of SUA was determined by applying receiver operating curve(ROC)analysis.The prognostic influence of SUA and other factors were studied by Kaplan-Meier curve as well as univariate and multivariate Cox proportional analysis.The influence of SUA on the predictive accuracy of IPI score was subsequently calculated using the Harrell’s concordance index(c-index).【Results】 1.167 cases of patients with DLBCL were collected.The median age at the time of SUA measurement was 60 years with a range of 7-86.53(31.7%)patients had high SUA(≥6.4 mg dl-1)while 114 had low SUA(<6.4 mg dl-1).Comparing low SUA group,High SUA level were signicantly associated with LDH and serum creatinine(p<0.001,p<0.001),age(p<0.001),B symptom(p=0.025),extranodal sites of disease(>1,p=0.046),and NCCN-IPI score(P=0.006).SUA level was negative related with Ann Arbor stage disease(Ⅲ/Ⅳ,p=0.081),bone marrow involvement(p=0.256),β2microglobulin level(p=0.281)and IPI score(p= 0.052).2.Among patients with the median follow-up time of 21(range,1-95)months,and median overall survival(OS)is 27(range,20-33)months.The 2-year OS and 5-year OS of the total patients is 50.9% and 20.9%.The 2-year OS and 2-year progression free survival(PFS)of the high SUA group is 26.3% and 22.6%.The 2-year OS and 2-year progression free survival(PFS)of the low SUA group is 26.3% and 22.6%.There were significant differences between the groups(P<0.001;P<0.001).3.Potential influences of OS and PFS in these patients were identified using univariate cox regression model.Analysis of a high SUA level(p<0.001),Ann Arbor stage disease(III/IV,p=0.031),presence of B symptoms(p<0.001),extranodal involvement sites(>1,p<0.001),an elevated LDH(p<0.001)and β2microglobulin level(p=0.003),high serum creatinine(p=0.001),IPI score(≥2,p<0.001)and NCCN-IPI score(≥6,p<0.001)were identified as poor prognostic factors for PFS;similar results were found for OS in our study cohort.4.To determine the independent prognostic parameters in DLBCL,multivariate analyses of PFS and OS were performed.For PFS,we observed that three variables including LDH(HR=3.681;95% CI 1.163-11.650,p=0.027),SUA(HR=3.851;95% CI 1.816-8.167,p<0.001)and NCCN-IPI(≥6,HR=4.861;95% CI 1.992-11.861,p=0.001)emerged as independent and significant predictors of increasing risk of cancer progression.For OS,similar findings were yielded.5.The estimated concordance index,using IPI stratification measures(0.777),improved to 0.837 when SUA was integrated in.【Conclusions】 In the present study,we concluded that increased SUA level at diagnosis is an independent predictor for worse clinical outcome in DLBCL patients.Integrating SUA to the IPI score might improve the survival prediction and risk stratification.