| Objective: To analyze and compare the clinical efficacy and safety of CD25 monoclonal antibody(basiliximab)and CCR5 antagonist(maraviroc)combined with conventional GVHD prophylaxis in the treatment of acute myeloid leukemia(AML)with unrelated allogeneic hematopoietic stem cell transplantation,and provide safer and more effective GVHD prophylaxis for AML after unrelated hematopoietic stem cell transplantation.Methods: This was a single-center,retrospective analysis of patients with AML or MDS-AML who underwent unrelated allo-HSCT from July 2014 to July 2018,all patients received basiliximab or CCR5 antagonist maraviroc for GVHD prophylaxis combined with CSA/MTX.All 60 patients were divided into three groups according to the different GVHD prophylaxis.32 patients receiving CD25 monoclonal antibody combined with conventional GVHD prophylaxis in CD25 monoclonal antibody group;20 patients receiving the CCR5 antagonist maraviroc combined with conventional GVHD prophylaxis in the maraviroc group;8 patients receiving CD25 monoclonal antibody and maraviroc combined with conventional GVHD prophylaxis in the maraviroc combined CD25 monoclonal antibody group.We primarily evaluated post-transplantation hematopoietic reconstrution,cumulative incidence of aGVHD,cumulative incidence of cGVHD,cumulative incidence of 100-day transplant-related mortality(TRM),1-year transplant-related mortality(TRM),2-year relapse rate(RR),2-year overall survival(OS),2-year disease-free survival(DFS)among three groups.For the 43 patients with CR1 and CR2 before transplantation,we performed a subgroup analysis in terms of post-transplantation cumulative incidence of OS,DFS and RR of the maraviroc group,CD25 monoclonal antibody group and maraviroc combined with CD25 monoclonal antibody group.Results: The median age was 31.5(range 14-59),31.5(range 14-64)and 29(range19-39)in the maraviroc group,the CD25 monoclonal antibody group and the maraviroc combined with the CD25 monoclonal antibody group.There was no statistically significant difference in terms of age in the three groups(P=0.326).The percentage of patients in the three groups with CR1 before allo-HSCT was 45%,65.6% and87.5%.The percentage of patients with CR2 or CR3 was 20%,9.4% and 0.Thepercentage of patients with NR or RL was 35%,25% and 12.5%.No significant difference was observed in the disease status in the three groups.The median follow-up time was 34.4 months(range 0.3-45months),13.3 months(range 1.5-51months),and16.8 months(range 0.3-21months)in the three groups,respectively.Neutrophils were at post-transplantation 13-15 days(median 14 days)in the maraviroc group,11-18 days(median 14 days)in the CD25 monoclonal antibody group,and 12-20 days(median 14days)in the maraviroc combined with the CD25 monoclonal antibody group,respectively.Platelets were at post-transplantation 7-22 days(median 14 days)in the maraviroc group,10-25 days(median 13 days)in the CD25 monoclonal antibody group,and 12-40 days(median 14 days)in the maraviroc combined with the CD25 monoclonal antibody group,respectively.No significant difference was observed in the engraftment of neutrophils and platelets in the three groups(P> 0.05).The cumulative incidence of grade II-IV aGVHD by the day 100 in the maraviroc group,the CD25 monoclonal antibody group,and the maraviroc combined with the CD25 monoclonal antibody group was 100%,43.75%,and 12.5%,respectively.Notably,maraviroc-treated patients had reduced risk of acute grade 2-4 GVHD by the day 100,compared with the other two groups(P=0.017).However,the cumulative incidence of post-transplantation 100-day acute grade 3-4 GVHD(5%、28.13% and 12.5%),chronic GVHD(40%、59.38% and25%),extensive cGVHD(35% 、 34.38% and 25%)were similarly among the three groups(P=0.103 、 0.150 and 0.871).Multivariate analysis demonstrated that GVHD prophylaxis containing maraviroc was an independent factor preventing acute grade 2-4GVHD by the day 100 after transplantation(HR:2.413,95%CI:1.041-5.595,P=0.04).There were no statistically significant differences in 100-day TRM(10%,18.7% and12.5%,P=0.687),1-year TRM(15%,21.9% and 25%,P=0.785),RR(40%,28.1% and12.5%,P=0.350),2-year OS(50.0%,43.8%,and 75%,P=0.297)and 2-year DFS(45%,37.5%,and 62.5%,P=0.486)among the three groups.The analysis of the subgroup of CR before transplantation showed that there was no significant difference in OS,DFS,RR among the maraviroc group,the CD25 monoclonal antibody group and the maraviroc combined with the CD25 monoclonal antibody group(P=0.324,0.867,0.496).Conclusion: CD25 monoclonal antibodies and CCR5 antagonist are safe and effective for GVHD prophylaxis after allo-HSCT of AML.Compared to CD25 monoclonalantibodies,CCR5 antagonists can notably reduce the incidence of acute 2-4 GVHD.In the mean time,it has the tendency to reduce the incidence of acute 3-4 GVHD and chronic GVHD without increasing TRM or RR.There are some limitations in this retrospective study,Therefore,the results are being examined in a multicenter randomized study. |
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