Factors Affecting IPI Score,Treatment Effect And Prognosis In Patients With Diffuse Large B-cell Lymphoma

Non-Hodgkin's lymphoma(NHL)is one of the leading causes of death in cancer patients,and diffuse large B cell lymphoma(DLBCL)is the most common subtype of NHL.Regardless of the classic cell-of-origin(COO)classification,DLBCL has extremely high molecular heterogeneity.Despite the high molecular heterogeneity of DLBCL,the current standard method for clinical treatment of DLBCL is still immunochemotherapy,namely R-CHOP(Rituximab/R,Cyclophosphamide/C,Doxorubicin/H,Changchun Necine/O and Prednisone/P).Currently,although 60%of DLBCL patients can be cured through the R-CHOP regimen,40%of patients eventually develop relapsed or refractory disease,and even cause disease progression or death.At present,actively seeking and exploring new clinical parameters and biomarkers to better stratify the risk of DLBCL patients,so as to achieve early judgment of disease progression or predict the treatment effect,are the key issues of hematologists.Given the apparent heterogeneity of DLBCL,reliable prediction tools are essential to optimize patient treatment strategies and care.In addition,accurate prognostic assessment helps to facilitate communication between doctors and patients,helps guide the initial treatment plan,and obtains the maximum therapeutic effect.Since 1993,the International Prognostic Index(IPI)has been the main prognostic model for patients with DLBCL.Because IPI relies on readily available clinical information,and its predictive power has been further validated in multiple studies.As a result,IPI has been widely accepted and recognized by clinicians for use in determining the severity of the disease.Therapeutic effects and progression-free survival(PFS)are one of the important indicators used in clinical evaluation of drug treatment strategies.At present,although more studies have identified the risk factors that affect the treatment effect and prognosis of DLBCL patients,the mortality and disease progression of DLBCL patients are still at a high level.For example,for patients who relapse within one year after R-CHOP,the survival rate is extremely low,with only 15%of patients receiving a durable response.Therefore,it is necessary to explore the clinical parameters and biomarkers that can confirm the characteristics and stratification of patients with DLBCL.In this study,a prospective cohort study was conducted to explore factors related to the IPI score,treatment effect,and PFS of DLBCL patients,to refine the risk stratification of DLBCL patients,and to provide a theoretical reference for early prognosis of DLBCL patients.Part ?:Clinical features,inflammation,cytokines and IPI scores in patients with DLBCLObjective:To explore the relationship between clinical characteristics,inflammation,cytokines and IPI score in patients with DLBCL.Methods:A total of 171 consecutive patients with DLBCL who were first diagnosed in Ruijin Hospital Affiliated to Shanghai Jiaotong University from July 2015 to July 2017 were selected as the research subjects.Baseline characteristics of patients after admission were collected and IPI scores were assigned to the patients by a hematologist.In addition,the venous blood of the patients was taken to detect inflammation and cytokines.The results were compared and analyzed using SPSS 22 software and R software.Result:(1)There was a statistically significant difference in IPI scores between male and female patients(P<0.05);male and female patients' age,lactate dehydrogenase(LDH),ECOG score,presence or absence of extranodal violations,Ann Arbor staging,grouping,HBsAg,EBV,and number of extra knots were not significantly different(all P>0.05);(2)As the age increases,the IPI score also shows an upward trend(P<0.001);(3)Patients with elevated LDH tend to obtain higher IPI scores(P<0.001);(4)The higher the ECOG score,the lower the IPI score;(5)Patients with extranodal invasion had higher IPI scores than patients without extranodal invasion(P<0.001);(6)As the ANN ARBOR stage increases,the IPI score shows an upward trend(P<0.001);(7)IPI scores of EBV-positive patients were higher than those of EBV-negative patients(P<0.001);(8)With the rise of the IPI score,the concentrations of ESR and CRP are increasing,suggesting that the inflammation index is related to the IPI score;(10)As the IPI score increases,albumin and Hb levels tend to decrease,suggesting that nutritional status is related to the IPI score;(11)As the IPI score increases,the concentrations of ferritin and microglobulin also show an upward trend,suggesting that excessive secretion of ferritin and microglobulin is related to the severity of DLBCL disease.(12)The levels of IP-10,MCP-1,IL-15,IL-18,IFNr,TNF-?,monocytes,NK cell,PD-1+,HLADR+,and Tim3+increased as the IPI score increased(both P<0.05);(13)With the increase of the IPI score,Total T cell,Helper T cell and Treg cell showed a downward trend(all P<0.05).Conclusion:The IPI score is closely related to the nutritional status,inflammation indexes and cytokines of DLBCL patients,suggesting that the above indicators can be used clinically to further optimize the IPI score.Part II:Clinical characteristics,inflammation,cytokines,and the relationship between treatment effects in patients with DLBCLObjective:To explore the relationship between clinical characteristics,inflammation,cytokines and treatment effects in patients with DLBCL.Methods:A total of 171 consecutive patients with DLBCL who were first diagnosed in Ruijin Hospital Affiliated to Shanghai Jiaotong University from July 2015 to July 2017 were selected as the research subjects.After excluding related contraindications,all patients were given R-CHOP treatment plan,three weeks as a course of treatment,a total of 6-8 courses.After the end of the treatment cycle,explore the factors related to the effect of the treatment.Result:(1)Patients with elevated LDH have a higher risk of disease progression or death(P<0.05);(2)Patients with high ECOG scores are likely to increase the risk of disease progression(P<0.05);(3)The treatment effect of patients with extranodal invasion was significantly worse than that of patients without extranodal invasion(P<0.05);(4)The higher the Ann Arbor stage,the worse the treatment effect(P<0.05);(5)The treatment effect of group A patients was significantly better than that of group B patients(P<0.05);(6)The greater the number of extra knots,the worse the treatment effect(P<0.05);(7)The lower the albumin concentration,the higher the risk of disease progression or death(P<0.05);(8)The higher the level of CRP,the greater the risk of disease progression or death(P<0.05);(9)The higher the concentration of ferritin and microglobulin,the worse the treatment effect,and the higher the risk of disease progression or death(P<0.05);(10 The lower the vitamin D concentration,the worse the treatment effect(P<0.05);(11)A decrease in Hb concentration indicates a poor treatment effect(P<0.05);(12)The higher the levels of IP-10,MCP-1,IL-15,IL-18,IFNr,IL-12P20,TNF-?,Mature B cell,NK cell,PD-1+and Tim3+,the worse the treatment effect(all P<0.05);(13)The higher the levels of Total T cell and Helper T cell,the greater the patient's treatment benefit(both P<0.05).Conclusion:(1)The baseline characteristics of patients with DLB CL(including ANN ARBOR stage,number of extranodules,ECOG score)and nutritional status are closely related to the effect of treatment;(2)Inflammatory factors and cytokines in DLB CL patients have a significant impact on the treatment effect.In the clinical treatment,it is necessary to comprehensively consider the specific situation of the patient and give personalized treatment strategies.Part ? Relationship between clinical characteristics,inflammation and cytokines and PFS in patients with DLBCLObjective:To explore the relationship between clinical characteristics,inflammation,cytokines and PFS in patients with DLBCL.Methods:A total of 171 consecutive patients with DLBCL who were first diagnosed in Ruijin Hospital Affiliated to Shanghai Jiaotong University from July 2015 to July 2017 were selected as the research subjects.After the patients were given the standard treatment regimen,all patients were followed up.The end point of observation was PFS.Results:Univariate analysis showed that:(1)After an average follow-up of 407.16±240.52 days,PFS events occurred in 40 patients,the incidence rate was 25.64%(40/156);(2)Patients with elevated LDH were more likely to have PFS events than patients with normal LDH(P<0.05);(3)Patients who have had extranodal violations have a higher risk of PFS events(P<0.05);(4)The higher the Ann Arbor stage,the greater the risk of PFS events(P<0.05);(5)Patients in group B are more likely to have PFS events;(6)The greater the number of outbreaks,the greater the probability of PFS events(P<0.05);(7)Patients with higher IPI scores are more likely to have PFS events(P<0.05);(8)Patients with higher ESR and CRP concentrations are more likely to have PFS events(P<0.05);(9)The lower the albumin,vitamin D and hemoglobin(Hb)levels,the higher the risk of PFS events(P<0.05);(11)There was a positive correlation between ferritin concentration and WBC count and PFS events(P<0.05):(12)With the increase of IP-10,VEGF,IL-7,IL-18,IL-2,IL-12P20,TNF-?,lymphocytes,NK,PD-1+,OX40+,Tim3+and VISTA concentrations,the risk of PFS events also increased(all P<0.05);(13)With the increase of Total T cell,Helper T cell and Treg cell levels,the risk of PFS events decreased(all P<0.05).Kaplan Meier survival curve shows LDH,extranodal invasion,IPI score,ANN ARBOR staging,grouping,ESR,albumin,CRP,ferritin,vitamin D,WBC,Hb,VEGF,IL-7,IL-18,IL-12P20,TNF-?,NK,Tim3+,VISTA,Total T cell,Helper T cell and Treg cell are closely related to PFS events.The above factors were further analyzed in the COX proportional hazards model,and the results showed that:(1)LDH,Ann Arbor staging,CRP,ferritin,IL-12P20,TNF-?,Tim3+and VISTA are independent risk factors for PFS events(all P<0.05);(2)Albumin,vitamin D,Hb,Total T and Treg are protective factors of PFS events(all P<0.05).Conclusion:Our results show that:(1)LDH,Ann Arbor staging,CRP,ferritin,IL-12P20,TNF-?,Tim3+,and VISTA are independent risk factors for PFS events,which suggests that the above indicators should be given enough attention in clinical practice;(2)Albumin,vitamin D,Hb,Total T and Treg are protective factors of PFS events,suggesting that clinical practice needs to pay attention to the nutritional status and self-resistance of patients.