| Objective:This study aimed to investigate the clinical effects of PT-Cy combined with ruxolitinib and tocilizumab in the prevention of graft-versus-host disease(GVHD)after haploidentical allogeneic peripheral blood stem cell transplantation Methods:Haploidentical allogeneic peripheral blood stem cell transplantation was performed from January 1,2019 to March 1,2020.Pretreatment can be divided into three schemes according to different diseases and states:(1)pretreatment of CR status in patients with leukemia and hemophilic cell syndrome fludarabine phosphate for injection 40 mg/m2×5d(d-6?d-2)+busulfan 130mg/m2×1d(d-6)+melphalan 100mg/m2×1d(d-5);(2)Pretreatment of NR status in patients with leukemia and thalassemia:fludarabine phosphate for injection 40 mg/m2×5d(d-6 d-2)+busulfan for injection 130 mg/m2×2d(d-6?d-5)+melphalan 100mg/m2×1d(d-4);(3)Pretreatment of severe aplastic anemia:fludarabine phosphate for injection 40 mg/m2×5 d(d-6?d-2)+PT-Cy 300mg/m2×3d(d-6?d-4)+melphalan 120mg/m2×1d(d-3);Prevention of GHVD:PT-Cy 40mg/kgx2d(d+3-d+4)+tocilizumab 8mg/kgxld(d-1)+ruxolitinib(d-1?d+50 1 tablet in the morning and 1 tablet in the evening per day,d+50?d+1 10 1 tablet per day,d+110?d 180 half of tablet per day,halved with azoles)+cyclosporine ciclosporin 2mg/kg(d+5?d+99,d+100 starting reduction,and d+180 stopping medication,with cyclosporine serum concentration maintained at 200-400mg/ml)+mycophenolate 10mg/kg(d+5?d+35).The study was followed up until May 1,2020.Neutrophil recovery was defined as an absolute neutrophil count of at least 0.5×109/L at three continuous time points.Transfusion-independent platelet implantation was defined as a platelet count(not dependent on blood transfusion)of over 20×109/L for 3 consecutive days.The diagnosis and clinical classification of acute GVHD was based on the criteria of Mount Sinai Acute GVHD International Consortium(MAGIC),and the diagnosis of chronic GVHD was based on the 2014NIH consensus criteria.Results:1.56 patients(26 males and 30 females)aged 4 to 56 years old were enrolled in the study.The median age is 31 years old.Among them,there were 4 cases of AA,6 cases of thalassemia,31 cases of acute myeloid leukemia(20 cases of CR,11 cases of NR),13 cases of acute lymphoblastic leukemia(9 cases of CR;4 cases of NR)and 2 cases of hemophagocytic syndrome.2.In this study,a total of 56 patients were enrolled and 56(100%)were successfully transplanted.The median time of neutrophil recovery was 16 days(15.78±1.68 days)after transplantation.The median time of platelet recovery was 20 days(17.23±3.56 days).3.The incidence of aGVHD was 48%(27/56),the incidence of grade ? accounting for 25%(14/56),grade ? accounting for 10.7%(6/56),grade ? accounting for 7.1%(4/56),grade ? accounting for 5.3%(3/56).The incidence of aGVHD grade ?-?was 23%and grade ?-? was 12.5%.The incidence rate of cGVHD patients was 37%(21/56),including 17.8%(10/56)of mild patients,14.2%(8/56)of moderate patients,and 5.3%(3/56)of severe patients.4.In this study,1 patient died of aGVHD.6 patients developed the pulmonary infection,among whom 2 patients died of poor prognosis of pulmonary infection.12 patients had human cytomegalovirus infection or continuously increased virus copy number.8 patients had Epstein-Barr virus infection or continuously increased virus copy number.8 patients showed significant myelosuppression,among whom 1 patient died of cerebral hemorrhage caused by severe myelosuppression.One patient died of leukemia relapse during follow-up5.The non-relapse mortality(NRM)rate was 7%after treatment.The overall survival(OS)rate was 91%.Conclusion:The use of PT-Cy combined with ruxolitinib and tocilizumab on patients with transplantation can reduce the incidence of acute and chronic G VHD and achieve a high success rate of transplantation.The current observations are safe and valid but need to be validated in a larger cohort. |
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