Aplastic anemia is a blood disease caused by the destruction of a person’s normal bone marrow cells by specific white blood cells known as T-lymphocytes. One of the treatment options is to give the patient medications that suppress the immune system, specifically the T-lymphocytes. The best immunosuppressive therapy for patients with severe aplastic anemia (sAA) is a combination of anti-thymocyte globulin (ATG) and cyclosporine (CsA). Combining these two drugs results in response rates of 60-75%. Two types of ATG are currently available. One derived from the horse, known as horse ATG (hATG), and the second derived from the rabbit, known as rabbit ATG (rATG). Both types have been successfully used in combination with CsA. Horse ATG is still in use in the United States. In Europe, hATG is no longer available. It was withdrawn from the market in 2007. There are recent studies which have shown poorer response rates and decreased survival in patients who have been treated with rATG as compared to hATG1 , while other studies show no difference in the results.2
A study spearheaded by Dr. Judith Marsh and the members of the European Group for Blood and Marrow Transplantation (EBMT) Severe Aplastic Anemia Working Party was conducted to help provide additional answers as to which type of ATG has a more positive response when initially treating patients with newly diagnosed sAA. This study is a Phase 2, non-randomized, prospective, open label multicenter study. In general, a Phase 2 study is a clinical trial whereby a drug is given to a patient with the intent of knowing whether the patient will respond to the therapy. This type of study also provides additional information to the investigators regarding the safety of the drug. Non-randomized means that patients were not randomly assigned to either group. Open-label indicates that the patient and the physician know which drug is being given. The study included 35 patients with sAA who were treated with rATG. The results were then compared with 105 patients from the EBMT registry who received hATG. The study indicated that none of the patients who received rATG achieved a complete response at 3 months. At 6 months only 3% of the patients achieved a complete response and 37% achieved a partial response. Further comparison of rATG to hATG showed the best total response of 60% for rATG versus 67% for hATG. The survival of patients at 2 years was less in those who received rATG (68%), as compared to those who received hTAG (86%). Additional analysis indicated that treatment with rATG at older than37 years of age negatively affected survival. In conclusion, the study showed treatment with rATG in combination with CsA resulted in lower response rates and survival rates as compared to treatment with hATG in combination with CsA.
1) Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, Young NS. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med. 2011 Aug 4;365(5):430-8. PubMed PMID: 21812672
2) Afable MG 2nd, Shaik M, Sugimoto Y, Elson P, Clemente M, Makishima H, Sekeres MA, Lichtin A, Advani A, Kalaycio M, Tiu RV, O'Keefe CL, Maciejewski JP.