The Clinical Study Of PTCY And CCR5 Antagonist Based GVHD Prophylaxis In Allogeneic Hematopoietic Stem Cell Transplantation

Objective:To investigate the safety and efficacy of PTCY and CCR5 antagonist(Maravioc)based GVHD prophylaxis in allogeneic hematopoietic stem cell transplantation.Methods:Retrospective analysis was performed from January 2015 to October2018,and the patients were continuously treated with PTCY and CCR5 antagonist which is based Sibling and Haplo hematopoietic stem cell transplantation case data of38 patients with hematopoietic malignancy.38 patients were divided into three groups according to the GVHD prevention regimen:In the first group,haplotype transplantation,Haplo Maraviroc+PTCY+FK506/MMF was used as the GVHD prevention regimen and short for Haplo Maraviroc PTCY group.In the second group,sibling transplantation,the GVHD prevention regimen was Maraviroc+PTCY,short for Sibling Maraviroc PTCY group.The third group,Sibling transplantation,GVHD prevention regimen was Maraviroc+CSA/MTX,short for Sibling Maraviroc CSA/MTX group.Absolute neutrophil count(ANC)and platelet implantation,acute graft-versus-host disease(aGVHD)and chronic graft-versus-host disease(cGVHD),overall survival(OS),disease-free survival(DFS),recurrence rate(RR),transplant-related mortality(TRM)were observed in the three groups.Results:The median ages of Haplo Maraviroc PTCY group,Sibling Maraviroc PTCY group and Sibling Maraviroc CSA/MTX group were:41.5(19-64),34(17-58)and47(27-55),P=0.115.There were 14 patients in Haplo Maraviroc PTCY group,including8 females and 6 males,8 patients with AML,4 patients with ALL,1 patient with MDS-EB1 and 1 patient with CMML.There were 11 patients in Sibling Maraviroc PTCY group,including 3 females and 8 males,1 patient with AML,1 patient with ALL,1 patient with MDS-EB2,1 patient with MDS-MLD and 1 patient with CML.There were 13 patients in Sibling Maraviroc CSA/MTX group,including 5 females,8 males,6patients with AML,4 patients with ALL,2 patients with MDS-EB1 and 1 patient with MDS-EB2.Pretransplant disease status of the three groups:Patients with first complete response(CR1)in Haplo Maraviroc PTCY group,Sibling Maraviroc PTCY group,and Sibling Maraviroc CSA/MTX group were 7 cases(50%),5 cases(33.3%)and 11 cases(84.6%),respectively.Patients with secondary complete response(CR2)were 2 cases(14.3%),2 cases(13.3%)and 2 cases(15.4%),respectively.Relapsed or non-remission(NR)patients were 5 cases(35.7%),4 cases(36.4%)and 0 cases,respectively.The disease status of the three groups before transplantation was statistically different(P=0.039).Hematopoietic implantation in the three groups:The median implantation time of absolute neutrophil count(ANC)≥0.5 x 10~9/L in Haplo Maraviroc PTCY group,Sibling Maraviroc PTCY group,and Sibling Maraviroc CSA/MTX group was 15(12-19)days,14(12-15)and 13(11-20)days,respectively.The median implantation time of platelet(PLT)≥20 x 10~9/L in the three groups was 18(12-26)days,15(12-17)and 13(8-18)days,respectively.There was no significant difference in the median implantation time of ANC and PLT between the three groups(P>0.05).The median follow-up time of Haplo Maraviroc PTCY group,Sibling Maraviroc PTCY group,and Sibling Maraviroc CSA/MTX group was 9.4(1.4-17.6),9(2-24)and 15(4.5-44)months,respectively.The cumulative incidence of II-IV aGVHD was 14.3%,18.2%and 15.4%(P=0.982)in the three groups at 100 days after transplantation,with no statistical difference.The cumulative incidence of III-IV aGVHD was 7.1%,9.1%and 7.7%(P=0.985),with no statistical difference.The cumulative incidence of cGVHD in the three groups was 21.4%,45.5%and 46.2%(P=0.372),respectively.And the cumulative incidence of extensive cGVHD was 7.1%,9.1%and 15.4%(P=0.791),respectively,with no statistical difference.To investigate the effect of HLA on aGVHD and cGVHD,it was found that the cumulative incidence of II-IV and III-IV aGVHD was 14.3%vs16.7%and 7.1%vs 8.3%(P>0.05)at 100 days after transplantation for HLA-haploidentical and HLA-identical siblings.The cumulative incidence of cGVHD and extensive cGVHD at 1 year after transplantation was 21.4%vs 45.8%and 7.1%vs12.5%,respectively(P>0.05).The 1-year OS,DFS,RR and TRM of 38 patients were68.4%,60.5%,23.7%and 18.4%,respectively.The 1-year OS of patients in the Haplo Maraviroc PTCY group,Sibling Maraviroc PTCY group,and Sibling Maraviroc CSA/MTX group were 71.4%,63.6%and 69.2%,respectively(P=0.861).The 1-year DFS of patients in the three groups was 57.1%,54.5%and 69.2%,respectively(P=0.459).RR and TRM of the patients in the three groups were 28.6%,36.4%,7.7%(P=0.224)and 21.4%,9.1%,23.1%(P=0.737),respectively.There was no statistical difference in OS,DFS,RR and TRM among the patients in the three groups.Conclusion:The PTCY and CCR5 antagonist based GVHD prophylaxis is safe and effective in haplo and sibling transplantation of hematologic malignancies.Compared with the commonly used GVHD prevention regimen reported in the literature,the combined PTCY and maraviroc GVHD prevention regimen can significantly reduce the incidence of aGVHD and cGVHD,and do not increase the recurrence rate(RR)and transplant-related mortality(TRM).For sibling patients,especially those with poor disease status before transplantation,it is recommended to carefully choose PTCY as the prevention program of GVHD.Compared with foreign standard GVHD prevention regimens,the addition of maraviroc significantly reduced the incidence of acute GVHD,improved disease-free survival,and did not increase infection rates.Our study was a retrospective analysis with a limited number of cases,and the results need to be confirmed by a randomized controlled clinical trial with a larger sample size.