The Efficacy Of Different Doses Of Antithymocyte Globulin(ATG) In Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review

Objective: To systematically evaluate the effects of different doses of ATG on allogeneic hematopoietic stem cell transplantation in order to explore whether there is an optimal ATG dose range.In this paper,the incidence of GVHD(aGVHD,cGVHD),non-recurrence mortality(NRM),and infection-related mortality are the mainly outcome measures.Methods: The database of Pubmed,Medline,The Cochrane Library,Embase,Elsevier,CNKI(China National Knowledge Infrastructure),Wanfang,etc.was searched by computers and the full texts were acquired by manual searching.The search time ranged from 2001 to March 2018,and the language could be Chinese and English.At the same time,the two reviewers screened the literature and extracted literature data according to the literature inclusion and exclusion criteria,and the randomized controlled trials and cohort studies that met the requirements were included in the analysis.The incidence of GVHD,NRM,and infection-related mortality were used as observation outcomes,and stata software was used for data consolidation analysis.According to different ATG dose groups,the included studies were divided into two groups with ATG total doses ? 6mg/kg(low dose group)and >6 mg/kg(high dose group),and compared,to investigate the different effects of high and low doses of ATG on theincidence of aGVHD and cGVHD,non-recurrence mortality,and infection-related mortality in patients receiving allogeneic hematopoietic stem cell transplantation.Results: A total of eight studies were included in this study.Two randomized controlled trials and six cohort studies included 899 patients.The results of the systematic analysis were as follows: the incidence of aGVHD at grade II-IV and the incidence of aGVHD at grade III-IV in the high-dose group were statistically significant [RR = 1.419,95% CI(1.138,1.768)p = 0.002,RR = 1.568,95% CI(1.042,2.359),p = 0.031].The non-recurrence mortality and infection-related mortality in the low-dose group were statistically significant [RR = 0.544,95% CI(0.354,0.834),p =0.005,RR = 0.535,95% CI(0.348,0.822),p = 0.004].The incidence of cGVHD in both groups had no statistical significance [RR = 1.094,95% CI(0.926,1.291),p = 0.291].Conclusion: ATG total dose of more than 6mg/kg(high dose group)reduced the incidence of grade II-IV aGVHD and the incidence of grade III-IV aGVHD,ATG total dose of ? 6mg/kg(low dose group)can reduce the incidence of NRM,infection-related mortality.However,there was no significant difference in the incidence of cGVHD.In summary,the high-dose group and low-dose group had their advantages and disadvantages,and did not find an optimal ATG dose range for the above indicators.Finally,prospective,multicenter,randomized controlled trials were further substantiated,and ATG doses could be further refined for subgroup analysis.