| BACKGROUD Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is currently the most important method to cure hematological malignancies.Graft-versus-host disease(GVHD)is a common complication after allo-HSCT and a major factor affecting the efficacy of transplantation.Especially,The occurrence of cGVHD severely affects the patient's long-term survival and quality of life.The National Institutes of Health(NIH)updated its new consensus on diagnostic and grading criteria for cGVHD in 2014.The liver is one of the major target organs of GVHD after allo-HSCT.According to this diagnostic criteria,liver cGVHD is reclassified TBIL>3 mg/L as score 3 as and serves it as the boundary between score 0-2 and score 3.The researches and studies based on NIH 2005 Consensus about cGVHD at home and abroad was various,so as on NIH 2014 Consensus.However,it is rare to catch a research about liver cGVHD alone.Therefore,we,a single-research-center,gathered allo-HSCT cases for nearly five years to retrospectively analyze its clinical features and influencing factors of liver cGVHD that based on this new NIH 2014 Consensus.AIM To retrospectively analyze the incidence and influencing factors of liver cGVHD and Score 3 liver cGVHD after allo-HSCT according to NIH 2014 Consensus.METHODS From January 1st 2013 to June 30th 2017,we followed up patients who a allo-HSCT in our hospital and survived for more the 100days,gathering their clinical characteristic data.According to NIH 2014 Consensus,we identified and diagnosed liver cGVHD and reclassified Score 3 liver cGVHD.Then we analyzed their influencing factors by Fisher's exact analysis and Anova's analysis for univariate factors,when multivariate ones by logistic regression or Cox risk model.The definitions on liver dysfunction,infection(hepatitis virus,CMV,EB virus,sepsis,etc.),drug-induced liver damage were guided by their relevant guidelines and expert consensus.RESULTS Of the 542 patients in the study,63 cases which survival time less then 100 days and 60 cases whose clinical data collected incompletely were excluded.There are 419 cases based on NIH 2014 Consensus for retrospective analysis.The median follow-up time of the 419 patients included in this analysis was 1.4 years(101-1661 days),while the overall survival rate was 46.29%in 4.5 years,of which 206 cases(49.2%)had liver dysfunction.95 cases were consistent with the diagnosis of liver cGVHD,whose incidence rate was 14.01%(median onset time was 1.7 years).The 3-year cumulative incidence rate was 19.56%,when 5-year cumulative incidence was 22.43%.The 4.5-year overall survival rate was 77.6%.There were 22 patients with score 3 as risk score(Score3 liver cGVHD),which cumulative incidence rate was 5.28%(median onset time was 1.3 years),when its cumulative incidence was 9.74%in 3 years and was 20.0%in 5 years.However,its 4.5-year overall survival rate was only 49.2%.Divided 419 patients into two groups,a liver cGVHD(n=95)and a non-hepatic cGVHD(n=324),univariate analysis suggested that the sex difference(P=0.035),donor and recipient Affinities(P=0.000),Stem cell sources(P=0.000),ATG use(P=0.000)and DLI(P=0.000)were significantly correlated the occurrence of liver cGVHD.Multivariate analysis Only showed female donors were the independent risk factors for the development of liver cGVHD,when its HR was 2.317(P=0.005)and 95%CI was 1.291 to 4.159.Follwed,divided 419 patients into two groups as Score 3 liver cGVHD(n=22)and non-Score 3 liver cGVHD(n=397).The univariate analysis showed that there was a sex difference(P=0.004)and and liver aGVHD during the course was a significant correlation in Score 3 liver cGVHD.Multivariate analysis suggested that female donor was an independent risk factor for Score 3 liver cGVHD,with a HR of 4.485(P=0.020,95%CI.(1.269?15.849).Then,Score 3 liver cGVHD(n=22)and non-liver cGVHD(n=324)were divided into two groups for analysis.univariate analysis showed that there was a gender difference(P=0.010),GVHD protocol with ATG(P=0.026)and liver aGVHD during the course(P=0.014)were significant correlation.Multivariate analysis suggested that female donors,GVHD protocol with ATG and liver aGVHD during the course were both the independent risk factors for Score 3 liver cGVHD.when the HR of female donor were 0.195(P=0.040,95%CI 0.041-0.931),the HR of liver aGVHD during the course of the disease was 0.342(P=0.028,95%CI 0.132-0.891),the HR of GVHD protocol with ATG was 2.656(P=0.046,95%CI 1.019-6.923).CONCLUSIONS 1.According NIH 2014 Consensus,followed up the 419 cases with allo-HSCT in who had a median follow-up of 1.4 years in a single center,its the cumulative incidence of liver cGVHD was 14.01%,when its 3-years cumulative incidence was 19.56%and 5-year cumulative incidence was 22.43%.The 4.5-year overall survival rate was 77.6%.For Score3 liver cGVHD,the cumulative incidence of Score 3 liver cGVHD was 5.28%when it was 9.74%in3years 20.0%in 5 years.The overall survival rate was only 49.2%in Score3 liver cGVHD.This result is a large sample of the current domestic research on the factors and morbidity of liver cGVHD,and there are some differences with the results reported abroad.2.In the analysis of influencing factors,only female donors were found as independent risk factors for liver cGVHD.However,for Score 3 liver cGVHD,the use of ATG in GVHD prophylaxis,and liver aGVHD during the course was an independent risk factor for the occurrence of this disease.This result suggests that donors and GVHD prophylaxis options,and the liver aGVHD treatment affects the incidence and overall survival of liver cGVHD and even more severe liver cGVHD. |
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