Antithymocyte globulin

Observational studies

Antithymocyte globulin has recently been used to treat myelodysplastic syndrome. In a phase II trial eight anemic patients with myelodysplastic syndrome were treated with antithymocyte globulin 40 mg/kg/day over 4 days plus prednisone [ ]. The study was stopped early, according to a preset termination rule, because of lack of efficacy. Adverse effects included serum sickness (in all patients), transient neutropenia and thrombocytopenia, diarrhea, vomiting, and syncope with a generalized seizure.

Comparative studies

Basiliximab and short courses of antithymocyte globulin have been compared in a randomized study in patients at high risk of acute rejection or delayed graft function who received a renal transplant from a dead donor [ , ]. Patients taking ciclosporin, mycophenolate mofetil, and prednisone were randomly assigned to either rabbit antithymocyte globulin 1.5 mg/kg/day (n = 141) during transplantation (day 0) and on days 1–4 or basiliximab 20 mg (n = 137) on days 0 and 4. The primary end-point was a composite of acute rejection, delayed graft function, graft loss, and death. At 12 months, the incidence of the composite end-point was similar in the two groups. Basiliximab was associated with a higher incidence of acute rejection (26% versus 16%) and of acute rejection that required treatment with antibody (8.0% versus 1.4%). The two groups had similar incidences of graft loss (10.2% and 9.2%), delayed graft function (45% and 40%), and death (4.4% and 4.3%). Although the incidences of all adverse events, serious adverse events, and cancers were also similar in the two groups, the patients who received basiliximab had a lower incidence of infection (75% versus 86%) but a higher incidence of cytomegalovirus disease (18% versus 7.8%).

A comparison of 5-year results between antithymocyte globulin and equine antithymocyte globulin after kidney transplantation showed higher event-free survival (73% versus 33%), graft survival (77% versus 55%), and freedom from rejection (92% versus 66%) with antithymocyte globulin [ ]. There were no additional cases of cytomegalovirus infection after the first year (13% versus 33%). There were two cases of post-transplantation lymphoproliferative disorder (PTLD) with equine antithymocyte globulin, and antithymocyte globulin was associated with profound lymphopenia at 2 years.

In an open, randomized, multicenter study, antithymocyte globulin was compared with basiliximab induction therapy followed by delayed introduction of ciclosporin in renal-transplant patients (n = 105) of low immunological risk who were receiving mycophenolate mofetil and glucocorticoids [ ]. One-year patient and graft survival rates were 98% and 94% with basiliximab (n = 52) and 98% and 96% with antithymocyte globulin (n = 53). The incidence of biopsy-confirmed acute rejection was 9.6% with basiliximab and 9.4% with antithymocyte globulin. The number of patients who required dialysis after transplantation was 29% with basiliximab and 30% with antithymocyte globulin. Significantly more patients given antithymocyte globulin had cytomegalovirus infection, leukopenia, and thrombocytopenia.

Cardiovascular

Rabbit antithymocyte globulin (RATG) is recommended for central venous administration, and there is no evidence to justify the common practice of adding heparin to the infusion bag. However, evaluation of thrombocytopenia may be complicated by co-administration. A total of 330 central or peripheral courses of RATG in 288 patients resulted in nine cases of deep vein thrombosis [ ]. In five there were prior infusion-related reactions and heparin was not used. In most cases the venous thrombosis occurred near the site of the infusion. These results provide justification for adding heparin when RATG is infused, especially peripherally.