Investigation Of Prognostic Factors For Chinese Patients With Hodgkin Lymphoma

Background:It is highly important to identify Hodgkin lymphoma(HL)patients with different prognosis accurately,according to which a more appropriate therapy scheme could be made for individuals to increase the cure rate and avoid possible overtreatment.The International Prognostic Score(IPS)was a seven-factor score system widely applied to guide the choice of individualized risk-adapted therapy of advanced Hodgkin lymphoma(HL),which was developed in 1998 based on data of western patients treated before 1992.With the medical technology progressing rapidly over the past decades,patients' outcomes have improved obviously than before.The application value of IPS in Chinese patients treated in the contemporary era has not been evaluated.Methods:We conducted a retrospective study involving 208 previously untreated Chinese advanced HL patients admitted to Cancer Hospital Chinese Academy of Medical Sciences(CHCAMS)from 1999.1 to 2015.4.All the patients were treated with chemotherapy(ABVD regimen)with or without radiotherapy as the first-line treatment.Patients' baseline clinical and laboratory parameters were collected,and a follow-up was performed on all the patients for freedom-from progression(FFP)and overall survival(OS).The prognostic value of IPS and 7 factors of IPS were assessed in this population using log-rank testing and Cox proportional hazards models.This study was in compliance with the Declaration of Helsinki and was approved by the Medical Ethics Committee of CHCAMS.Results:With a median follow-up time of 79 months(range 15-210 months),the 5-year FFP and OS were 78.8%and 86.0%respectively,which improved obviously compared with the original IPS study(5-FFP,66%;5-OS,78%).The IPS remain prognostic for both freedom-from progression(FFP)(P=0.041)and overall survival(OS)(P=0.013),but the range narrowed obviously,with 5-year FFP ranging from 87.1%to 61.5%and 5-year OS ranging from 94.1%to 69.2%whereas the 5-year FFP ranged from 84%to 42%and the 5-year OS ranged from 89%to 56%in the original IPS study.The separation of survival curves was not as good as before,even some were overlapped(the 5-year FFP of score 1 was lower than score 0,85.2%vs.87.2%).Only two of the seven IPS factors showed significant independent prognostic value in the multivariate analysis:stage IV(for FFP,P=0.016;for OS,P=0.019)and hemoglobin<105g/L(for FFP,P=0.021;for OS,P=0.028).A simple prognostic score calculated by adding 1 point each for any of the two factors was prognostic both for FFP(P<0.001)and OS(P<0.001)significantly with the corresponding curves separating very well(5-year OS:score 0 91.5%vs.score 1 84.6%,p = 0.040,score 1 84.6%vs.score 2 68.8%,P<0.001),but the range still narrowed with 5-year FFP ranging from 85.9%to 58.2%and 5-year OS ranging from 91.5%to 68.8%.Conclusions:The IPS has decreased prognostic discrimination in Chinese advanced Hodgkin lymphoma patients treated in the contemporary era.Studies with larger sample size are needed to develop a new prognostic scoring system for contemporary Chinese patients,so as to identify populations with different recurrent risk accurately.Our findings need further validation.Background:The International Prognostic Score(IPS)was the traditional prognostic scoring system of advanced Hodgkin lymphoma(HL).However,the IPS had decreased utility in patients treated in the modern era.In recent years,there has been an increasing tendency of investigating new prognostic factors for HL.Serum beta-2 microglobulin(B2MG)has been found elevated in many lymphoid malignancies and elevated serum B2MG was associated with poorer prognosis.Programmed death ligand-1(PD-L1)has been found expressed in many malignancies and high level of PD-L1 was associated with poorer prognosis.Our study aim to evaluate the prognostic value of pretreatment serum B2MG level and PD-L1 expression level in classical HL(CHL).Methods:We conducted a retrospective study involving 202 previously untreated CHL patients admitted to Cancer Hospital Chinese Academy of Medical Sciences(CHCAMS)from 1998.5 to 2015.7.All the patients were treated with chemotherapy(ABVD regimen)with or without radiotherapy as the first-line treatment.Patients' baseline clinical and laboratory parameters were collected,and a follow-up was performed on all the patients for freedom-from progression(FFP),lymphoma-specific survival(LSS),and overall survival(OS).Tissue specimens of sixty-two patients were available in CHCAMS by screening patients from 2006.1 to 2015.7.Receiver operating characteristic(ROC)curve analysis was used to determine the optimal cutoff values of B2MG.The Chi-square test or Fisher's exact test was performed to compare the distribution of patient characteristics between different B2MG level groups for categorical variables and t test for continuous variables.The prognostic value of serum B2MG level was assessed in this population using Log-rank test and Cox proportional hazards models.This study was in compliance with the Declaration of Helsinki and was approved by the Medical Ethics Committee of CHCAMS.Results:1.With a median follow-up time of 85 months(range 12-218 months),the 5-year FFP,OS and LLS were 78.6%,88.3%and 90.2%respectively.The value of 2.5 mg/L was defined as the cutoff value.A serum B2MG level>2.5 mg/L was significantly correlated with an older age(P=0.005),a higher Ann Arbor stage(P=0.010),the presence of B symptoms(P=0.017),elevated lactate dehydrogenase(LDH)(P=0.035)and the constituent ratios of IPS scores were different in the two groups(P<0.001).As for the seven IPS factors,a serum B2MG level>2.5 mg/L was significantly associated with age?45 years(P=0.028),stage IV(P=0.003),hemoglobin<105g/L(P=0.009),WBC?15×109/L(P=0.006)and lymphocytopenia(P=0.012).In multivariate analysis,IPS>3 and B2MG level>2.5 mg/L have significant independent negative prognostic value for.FFP(5-FFP,86.0%vs 66.8%,HR=2.475,95%CI,1.230-4.978,P=0.011;5-FFP,89.7%vs 66.8%,HR=3.223,95%CI,1.651-6.292,P=0.001)and LSS(HR=2.316,95%CI,1.037-5.176,P=0.041;HR=2.633,95%CI,1.096-6.326,P=0.030).Only B2MG level?2.5 mg/L was independent prognostic factor for OS(HR=2.343,95%CI,1.064-5.159,P= 0.034).The combination of B2MG level and IPS identified a wider prognostic range(5-year FFP,91.1%to 50.7%)than IPS alone(90.9%to 62.3%)with a sizable number of patients in different risk groups,especially in patients with stage III/IV(5-year FFP,95.3%to 49.8%).2.With a median follow-up time of 71 months(range 16-123 months),the 3-year FFP,OS and LLS were 78.6%?88.3%and 90.2%respectively.In univariate analysis,IPS>3 and high expression of PD-L1 were adverse prognostic factors of FFP;Only IPS>3 was adverse prognostic factors of LSS.The 5-FFP of patients with high and low expression of PD-L1 was 59.5%and 86.6%respectively.Compared with patients with low expression of PD-L1,the number of patients with ag?45 years(P=0.028),stage IV(P=0.003)and lymphocytopenia(P=0.012)were larger in patients with low expression of PD-L1.But multivariate analysis showed only IPS>3 has independent prognostic significance for FFP and PD-L1 expression level didn't.Conclusions:In conclusion,our study suggested that pretreatment serum B2MG,a routine-detected index in clinical practice,was of great prognostic value in modern advanced CHL and the combination of IPS and B2MG confers stronger prognostic value than IPS alone.High level of PD-L1 was associated with poorer prognosis but it had no prognostic significance independent of IPS.A multi-center study with larger group of patients and longer follow-up time is needed to validate our findings.Background:It is highly important to identify Hodgkin lymphoma(HL)patients with different prognosis accurately,according to which a more appropriate therapy scheme could be made for individuals to increase the cure rate and avoid possible overtreatment.There is no consensus about the progn ostic system of early-stage HL worldwide and different institutions have different conclusions.Our study aims to investigate the prognostic factors in Chinese early-stage HL patients.Methods:We conducted a retrospective study involving 529 previously untreated early-stage HL patients admitted to Cancer Hospital Chinese Academy of Medical Sciences(CHCAMS)from 1999.1 to 2015.4.All the patients were treated with chemotherapy(ABVD regimen)with radiotherapy as the first-line treatment.Patients'baseline clinical and laboratory parameters were collected,and a follow-up was performed on all the patients for freedom-from progression(FFP),lymphoma-specific survival(LSS),and overall survival(OS).The prognostic factors were assessed in this population using Log-rank test and Cox proportional hazards models.This study was in compliance with the Declaration of Helsinki and was approved by the Medical Ethics Committee of CHCAMS.Results:With a median follow-up time of 96 months(range 20-217 months),the 5-year FFP,OS and LLS were 90.1%,98.2%and 96.7%respectively.According to the German Hodgkin Study Group(GHSG)or the European Organization for Research and Treatment of Cancer(EORTC)prognostic criteria,there was no significant difference between the favorable and unfavorable patients(GHSG:5-year FFP,93.4%vs.88.7%,p=0.195;5-year LSS,97.0%vs.96.5%,p=0.460;5-year OS,97.0%vs.95.9%,p=0.876.EORTC:5-year FFP,92.7%vs.88.3%,p=0.093;5-year LSS,97.5%vs.96.0%,p=0.094;5-year OS,97.5%vs.95.2%,p=0.081).Of all the factors of the GHSG or EORTC prognostic criteria,only mass has unfavorable prognostic significance for FFP(Hazard ratio(HR)= 1.690,95%Confidence interval(CI):1.010-2.830,p=0.046),only age?50 years has unfavorable prognostic significance for LSS and OS(HR=3.465,95%CI:1.408--8.554,p=0.007;HR=3.569,95%Cl:1.607-7.928,p=0.002).Elevated serum B2MG is the adverse prognostic factor for FFP,LSS and OS(5-year FFP,84.3%vs.93.4%,p=0.001;5-year LSS,93.7%vs.98.6%,p<0.001;5-year OS,92.2%vs.98.6%,p<0.001).Prognosis of patients achieving complete remission(CR)after 2 cycles of ABVD regimens is better than patients without CR(5-year FFP,98.0%vs.88.1%,p=0.001;5-year LSS,100%vs.95.9%,p=0.015;5-year OS,100%vs.95.3%,p=0.021).In addition,for favorable patients,there is no significant difference upon survival time between those receiving 2-3 cycles and those receiving 4-6 cycles of chemotherapy(5-year FFP,91.7%vs 93.6%,p=0.644;5-year LSS,97.6%%vs 97.5%,p=0.735;5-year OS,97.6%vs 97.5%,p=0.356)?Conclusions:In conclusion,our study suggested that the GHSG or the EORTC prognostic criteria had poor prognostic value in our patients.Elevated serum B2MG is an adverse prognostic factor.Mid-term efficacy of chemotherapy also has remarkable prognostic significance.In addition,for favorable patients,2-3 cycles of chemotherapy combined with radiotherapy may be sufficient.