| Background:Indolent B-cell non-Hodgkin lymphoma(B-iNHL)is a group of diseases which could be divided into Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma(CLL/SLL),Follicular Lymphoma(FL),Marginal Zone Lymphoma(MZL)and Lymphoplasmacytic Lymphoma/Waldenstr(?)m Macroglobulinemia(LPL/WM)via the clinical features of blood and bone marrow and progression process.So far the evaluation systems for treatment and prognosis mostly focus on clinical markers such as age,hemoglobin(HG),platelet counts(PLT)and β2-MG.Due to the long course of B-iNHL,some patients fail to stick to follow-up research.The lack of evaluation of diseases causes the poor prognosis.Therefore,finding more prognosis markers plays an important role in the diagnosis and treatment for long-term treatment for B-iNHL patients,which could help guide and adjust the following therapeutic schemes,especially to make individualized plans for each patient.Serum sialic acid(SA),which is a derivative of neuraminic acid widely distributed in mammalian cells,has been proved to be associated with metastasis and prognosis of malignant carcinomas.They mediate and modulate a variety of normal and pathological processes.They are principal factors influencing the half-life of glycoproteins in circulation.Sialic acid provides the structural basis for carbon-substrate complex formation.Serum acid serves for protection against pathogenic bacteria as well as a role in the progression of cell adhesion.Specific tumor characteristics were ascribed to the increased expression of sialic acid sugars on the surface of cancer cells,and this led to the definition of sialic acids as potential therapeutic targets.Recently more study has found that SA is also linked to the occurrence,development and prognosis of malignant tumors and acute inflammation.However,the prognosis value of SA in hematological diseases has not been found before.In this study,we evaluated the prognostic value of serum sialic acid concentration in newly diagnosed B-iNHL patients.Methods:In this retrospective study,a total of 345 B-iNHL patients were included from January 2011 to March 2020 at Shandong Provincial Hospital.We collected clinicopathological characteristics such as included age,gender,lymphoma Ann-Arbor stage(for CLL,Rai stage is included),the presence of B symptoms,WBC counts,hemoglobin,platelet(PLT)counts,lymphocyte counts,serum LDH levels,serum β2-MG,serum sialic acid concentration(SA)and explored the prognostic significance of SA in B-iNHL patients.The association of SA and overall survival(OS)and progression-free survival(PFS)was assessed in univariate analysis and multivariate Cox regression.Results:Among the 345 B-iNHL patients,176 CLL/SLL patients account for 51.0%,85 FL patients account for 24.6%,54 MZL patients account for 15.7%and 30 LPL/WM patients account for 8.70%.About 58.9%(n=203)of them were male and 41.4%(n=142)of them were female.The median age at diagnosis is 60 years old(range from 19-86 years old).The median follow-up time is 36 months(range from 1-85 months).By the time of the end of follow-up time,31 patients died and 45 patients presented progression or eventually died from progression.Elevated serum SA level was associated with poor survival and tumor progression in B-iNHL patients.Patients were divided with different SA level stratified by a cutoff value of 608.5mg/L.Shorter OS(p<0.001)and PFS(p<0.001)revealed that patients with higher SA level at diagnosis(>608.5mg/L)had worse prognosis than those with lower SA level(≤608.5mg/L).Multivariate analysis indicated that SA was significantly independent for both OS(HR,3.140;95%CI,1.691-5.831;p<0.001)and PFS(HR,2.134;95%CI,1.329-3.425;p=0.002)in B-iNHL patients.The shorter OS and PFS of patients with elevated SA were verified in subgroup analysis respectively.Compared to patients with SA≤608.5mg/L,those with elevated SA were associated with poor OS(p=0.0001;p=0.0128)and PFS(p=0.0037;p=0.0127)in CLL/SLL and FL patients separately.MZL patients with SA>608.5mg/L had worse PFS than those with SA≤608.5mg/L.Conclusion:1.In this retrospective study,we proved the prognostic value of SA in B-iNHL patients for the first time.SA was associated with shorter OS and PFS for B-iNHL patients.2.Elevated SA level at diagnosis was associated with advanced stage(stage Ⅲ/Ⅳ),the presence of B symptoms,lower WBC counts,lower lymphocyte counts,anemia and higher level of serum β2-MG.3.Univariate analysis revealed that advanced age,anemia,lower PLT counts,advanced stage of tumor(Ⅲ/Ⅳ),elevated LDH,elevated β2-MG level and higher concentration of serum SA level were correlated with shorter OS.4.As for PFS,univariate analysis revealed that advanced age,the presence of B symptoms,anemia,lower PLT counts,advanced stage of tumor(Ⅲ/Ⅳ),elevated LDH,elevated β2-MG and high concentration of serum SA level were correlated with worse PFS.5.Multivariate analysis indicated that SA was significantly independent for both OS and PFS in B-iNHL patients.The shorter OS and PFS of patients with elevated SA were verified in subgroup analysis respectively.6.As for sub-group analysis,compared to patients with lower serum SA level,those with elevated SA were associated with poor OS and PFS in CLL/SLL and FL patients separately.MZL patients with higher SA level had worse PFS than those with lower SA level.Serum SA level was not significantly associated with OS in MZL patients and OS and PFS in LPL/WM patients. |
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