Anti-thymocyte globulin for treatment of T-cell-mediated allograft rejection

Table 2 Summary of non-randomized clinical studies

No	Ref.	Study design	ATG -dose/duration	Graft outcome	Death	Adverse events
1	Hardy et al[60], 1980	Prospective, non-randomised, single centre , United States, n = 20 (10 ATG)	eATG – 15 mg/kg (max 750 mg) for 21 d + MP (750, 200 & 150 mg for 3 d) (n = 10) vs MP (750, 200 & 150 mg for 3 d) (n = 10)	Reversal – 9/10 (ATG) vs 8/10 (control); Recurrent rejection 2/10 (ATG) vs 4/10 (control); Graft loss at 12 mo – 4/10 (ATG) vs 5/10 (control)	0 in both groups	3 serious complications in control group and 1 in ATG
2	Richardson et al[30], 1989	Prospective, non-randomised, single centre, United Kingdom	rATG (2-3 mg/kg for 5-10 d) reduced to 1-2 mg/kg if leukopenia or thrombocytopenia (n = 27)	70.3% graft survival with mean follow-up time of 13.3 mo; 8 out of 27 failed (6 due to rejection, 1 death, and 1 renal artery stenosis)	1 death	6 UTIs, 1 pseudomembranous colitis, 8 CMV and 5 HSV, 2 deaths
3	Clark et al[45], 1993	Prospective, non-randomised, single centre, United Kingdom	Group 1: rATG, 2.5-5 mg/kg/d) for 10-14 d (n = 10); Group 2: As per T cell count for 10-14 d (n = 17)	76% graft survival at 1 year group 2 (vs 60% in group 1); Group 1 – (4 rejections); Group 2 – (4 rejections)	2 deaths (group 1) vs 0 deaths (group 2)	Group 1: 3 serious viral infection, 6 minor infections; Group 2: 11 minor infections
4	Uslu et al[61], 1997	Retrospective, non-randomised, single centre, Turkey	rATG 5 mg/kg for 13.7 ± 3.7 d (n = 9) OKT3 5 mg/d for 11.4 ± 1.9 d (n = 5)	Graft survival: 78% ATG vs 20% OKT3 with median f/u 405 d		OKT3 – 1 CMV, Fever > 38 in 80% pts in both groups, Leukopenia (35% ATG vs 0 in OKT3)
5	Sharma et al[46], 2003	Prospective, non-randomized, single centre, India	ATG 1.5-1.8 mg/kg alternate d, mean duration 5 doses (n = 33)	90% graft survival in first year and 73% at 20 mo. Graft loss in 4; Recurrent rejection in 8/33 at 3 mo	1 death	11 pneumonia, 3 UTI, 1 peritonitis, 2 CMV, 5 leukopenia
6	Colak et al[62], 2008	Retrospective, non-randomised, single-centre, Turkey	ATG 3-5 mg/kg/d 10-14 d (Dose adjusted with other parameters) (n = 23)	Graft function improved in 19 cases (83%)	1 death	9 infections (3 pulmonary aspergillosis, 2 CMV, 4 pulmonary/urinary bacterial infections)
7	Kainz et al[33], 2009	Retrospective, non- randomised, multi centre, Austria	N/A n = 399 (368 ATG, 31 OKT3)	Median actual graft survival 9.5 yr ATG vs 4.5 yr OKT3	N/A	N/A
8	van der Zwan et al[38], 2018	Retrospective, non-randomised, single centre, Netherlands	rATG – 4 mg/kg repeated after 4 d if CD3 > 200, for 2 wk (n = 103)	Median allograft survival 7.0 yr. At one yr 78.2% had functioning graft; At 5 yr 55.6% functioning graft; 49 lost graft in median f/u 6.8 yr	17 deaths	97 bacterial, 8 fungal, 27 CMV reactivation, 4 EBV reactivation, 6 BK viraemia), 14 malignancy (12 solid, 2 lymphoma)

ATG: Anti-thymocyte globulin; EBV: Epstein-Bar virus, CMV: Cytomegalovirus, rATG: Rabbit anti-thymocyte globulin; OKT3: Muromonab CD3, UTI: Urinary tract infection; N/A: Not applicable.