Comparison Of Two Different Doses Of Antithymocyte Globulin In Conditioning Regimens For Haploidentical Hematopoietic Stem Cell Transplantation

Objective:Antithymocyte globulin(ATG)as a part of conditioning regimen has been used for GVHD prophylaxis and shown significant clinical efficacy,but the optimal dose of ATG remains unclear.We analyzed the effects of 10mg/kg and 7.5 mg/kg ATG to provide the rationale for identification of the optimal doseMethods:From March 1,2013 to October 14,2019,one hundred patients with hematologic malignancies were enrolled,who firstly underwent haploidentical hematopoietic stem cell transplantation(haplo-HSCT)with myeloablative conditioning.We retrospectively compared the effects of 10 mg/kg and 7.5 mg/kg ATG(rabbit anti-human thymocyte immunoglobulin,thymoglobulin),using SPSS and R software to perform statistical analyses.Results:59 and 41 patients were enrolled in the ATG-10 and the ATG-7.5 groups,respectively.The median time to achieve myeloid engraftment was 12 days(range,6-20 days)and 12 days(range,10-21 days),respectively(p=0.91).And the median time to platelet engraftment was 13 days(range,10-56 days)and 12 days(range,8-39 days),respectively(p=0.08).No significant difference was observed between the two groups,regarding the cumulative incidences of grade Ⅱ-Ⅳ acute GVHD(15.3%vs:14.6%;p=0.93),grade Ⅲ-Ⅳ acute GVHD(1.7%vs 9.8%;p=0.07)and 3-year chronic GVHD(12.1%vs 14.3%;p=0.77).The 3-year cumulative incidence of relapse was 18.4%and 31.0%in the two groups,respectively(p=0.22).In the multivariate analysis,the dose of ATG did not influence the risk of relapse,while the status of not complete remission before HSCT was associated with high risk of relapse(HR=3.04,95%CI=1.10-8.45,p=0.03).The incidence of 3-year overall survival was 68.9%vs 73.5%(p=0.98)and of the 3-year GVHD-free/relapse-free survival was 66.7%vs 53.1%(p=0.14)in the ATG-10 and ATG-7.5 groups,respectively.Additionally,the ATG-7.5 group had a trend of lower cumulative incidence of hemorrhagic cystitis(24.4%vs 40.7%,p=0.07),but the difference was not statistically significantConclusions:Decreasing the dose of ATG from 10 mg/kg to 7.5 mg/kg did not compromise the prevention of GVHD and had no influence on relapse and survival Moreover,7.5 mg/kg ATG tended to decrease the incidence of hemorrhagic cystitis Collectively,ATG at a total dose of 7.5 mg/kg should be considered as a part of conditioning regimen in haplo-HSCT.