| Background:Chronic graft-versus-host-disease(cGVHD)is one of the main complications after allogeneic hematopoietic stem cell transplantation(Allo-HSCT).The incidence of cGVHD is about 50%after HSCT.It can involve multiple organs including skin,eyes,mouth,gastrointestinal,liver,lung,joints and fascia,etc.Therefore,refractory cGVHD seriously affects the survival and quality of patients'lives.In terms of treatment,some refractory cGVHD did not respond well to conventional first-line and second-line treatments,so it is necessary to explore a new approach.And sirolimus(SRL),as a kind of mTOR inhibitor,can not only exert immunosuppressive effect,but also have anti-tumor,anti-fibrosis,anti-virus effect,etc.Besides,it also has low hepatorenal toxicity.That means SRL has special advantages in the treatment of cGVHD.At present,the relevant studies at home and abroad are mainly retrospective studies,suggesting that sirolimus-based regimens are effective for refractory cGVHD.However,since most of the studies were published early,new evaluation criteria were not used to evaluate the efficacy.Objective:To evaluate the efficacy and safety of SRL combined regimen in the treatment of refractory cGVHD,and to explore the better regimen for the treatment of refractory cGVHD.Methods:We performed a retrospective analysis of 42 patients who receive SRL combined regimen in the treatment of refractory cGVHD from November 2016 to May 2019 in department of hematopathology of Nanfang Hospital.According to the 2014 NIH cGVHD severity score,we assess the severity score of different organs and the overall condition.The score before treatment will record as baseline,then score at the first and every 3 months after treatment,the scores will be compared with the baseline,and serious adverse events will be recorded to evaluate the efficacy and safety of SRL.Result:Among the 42 effective consecutive cases,31 were males and 11 were females,with a median age of 36 years.Primary disease included AML(17 cases),ALL(16 cases),CML(3 cases),MDS(5 cases),and lymphoma(1 case).In terms of transplant method,HLA matched PBSCT was used in 33 patients,8 patients were HLA partially matched BMT+PBSCT,and 1 patient was HLA partially matched PBSCT.8 cases of cGVHD were progressed by aGVHD,and the remaining 34 cases were directly generated after transplantation.In terms of treatment effect,30 patients responded to the treatment,including 11 patients revealed complete remission(CR),12 patients revealed partial remission(PR)and 7 patients revealed stable disease and treatment reduction(SD1),overall complete remission rate(CRR)was 26.19%,overall response rate(ORR)was 71.43%.After SRL combined regimen,the overall severity of cGVHD was alleviated compared with that before treatment(p=0.001),and the number of organs involved was reduced compared with that before treatment(p=0.001).The cumulative ORR reached a peak at 6 months(84.38%)after SRL combined regimen,then came to a downward trend.By analyzing the therapeutic effect of various organs involved in cGVHD,it can be seen that the response rate(RR)of SRL combined regimen in the treatment of skin,mouth,eyes,gastrointestinal tract,liver,lung,joints and fascia cGVHD was 57-100%,and the curative effect of genital cGVHD needed further study due to the small number of cases included.In terms of survival situation,the median follow-up time was 18 months,among the 42 patients,7 patients died and the rest survived,the one-year overall surivival(OS)was 87.2%,and the two-year OS was 63.1%.The one-year GVHD-free and relapse-free survival(GRFS)was 60.6%.No serious drug-related adverse reactions occurred during treatment.Conclusion:From the perspective of condition of overall and every organs cGVHD,the SRL combined regimen can improve refractory cGVHD in a certain extent,and the maximum benefit may be obtained at the 6th month of treatment.The whole process of medication is safe and has a certain application prospect. |
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