Clinical Study Of Combined Use Of Post Cyclophosphamide And Post Anti Thymocyte Globulin In The Prevention Of GVHD After Haplo-HSCT

[Objective]To investigate the clinical efficacy of combined use of cyclosporin,enzyme phenol ester,cyclophosphamide and anti thymocyte globulin after haploid allogeneic peripheral blood stem cell transplantation to prevent graft-versus-host disease.[Methods]The study was divided into control group A and experimental group B.A group was a retrospective study.Group B was a non randomized prospective study.(1)group A:57 patients with haploid allogeneic peripheral blood stem cell transplantation from December 2011 to August 2015 in Kunming General Hospital of the PLA were selected.There were 22 cases of acute non lymphocytic leukemia(AML),10 cases of acute lymphoblastic leukemia(ALL),3 cases of chronic myelocytic leukemia(CML),1 cases of chronic lymphocytic leukemia(CLL),13 cases of severe aplastic anemia(SAA),3 cases of β-thalassemia,1 cases of multiple myeloma(MM),and 1 cases of non Hodgkin lymphatic lymphnodes(NHL).Non lymphocytic system preconditioning methods:Intravenous drip of fludarabine 40mg/m2 from-7d to-2d,infuse Busulfan 130mg/m2 from-5d to-2d;Lymphocytic system preconditioning methods:oral Semustine.300mg/m2 in-8d-infuse Fludarabine from-7d to-2d,infuse Melphalan 50mg/m2 from-5d to-2d.Prevention method of GVHD:infuse Cyclophosphamide 1.8g/m2 from +3d to +4d,use Anti thymocyte globulin 2.0mg/m2 from +5d to +6d,oral Mycophenolate Sodium Enteric-coated Tablets 10mg/kg,totally 30mg/kg/d from +7d to +180d,infuse Cyclosporin 2 to 5mg/kg from+7d to +180d.(2)Group B:42 patients with haploid allogeneic peripheral blood stem cell transplantation from September 2015 to January 2018 in Kunming General Hospital of the PLA were selected,including 12 cases ALL,7 cases AML,4 cases CML,3 cases of acute mixed cell leukemia(CR2,NCR1),MDS(RAEB2),MM2,Haemophilus blood cell syndrome(HLH)in 2 cases,SAA6 cases,and severe beta thalassemia 4 cases.the preconditioning methods is same as group A.Group B GVHD prevention plan added anti thymocyte globulin(ATG)on the basis of group A,and the specific usage was intravenous drip ATG2mg/kg in +5d and +6d.[Result]Group A:55 patients(96%)were successfully implanted in 57 patients,and the median time of granulocyte implantation was 13d,and the median time of platelet implantation was 15d.Group B:41 cases(97.6%)were implanted in 42 patients,40 cases of platelet implantation(95.2%),1 cases of primary thrombocytopenia(2.4%),1 cases of secondary platelet implants(2.4%).1.The occurrence of aGVHD in group A and group B:Grade Ⅱ-Ⅳ aGVHD40.3%vs 26.2%(p<0.05),grade Ⅲ-Ⅳ aGVHD 17.5%vs 11.9%(P>0.05);cGVHD 22.8%vs 16.7%(P>0.05),extensive cGVHD 15.8%vs 4.8%(p<0.05)3.Transplantation related complications:oral mucositis:15.8%vs 21.4%(P>0.05),20.3%vs 19.0%of gastrointestinal mucositis(P>0.05),acute hemorrhagic cystitis 21.4%vs 19.0%(P>0.05),delayed hemorrhagic cystitis 22.8%vs 26.2%(P>0.05),3.5%vs 3.2%of hepatic vein occlusion(P>0.05),0%vs 0%of cardiovascular complications(P>0.05),and 5.2%vs 9.5%in nervous system complications(P>0.05).4.infection:Breakthrough pulmonary fungal infection 24.6%vs28.6%(P>0.05);intracranial infection 7.0%vs7.1%(P>0.05).5.Recurrence rate,OS,DFS and NRM:The recurrence rate was 22.8%vs 16.7%(P>0.05),OS68.4%vs 69.0%(P>0.05),NRM24.6%vs26.2%(P>0.05),and mortality rate 31.6%vs 30.9%(P>0.05).[conclusion]The combined use of cyclophosphamide and anti thymocyte globulin to prevent graft-versus-host disease after haploid allogeneic peripheral blood stem cell transplantation is better than post transplant cyclophosphamide.