A prospective randomized controlled study on the efficacy and tolerance of two antilymphocytic globulins in the prevention of rejection in first-heart transplant recipients

Abstract

The usefulness of induction phase treatment in heart transplantation is a long-standing debate in the literature. Several centers report good short-term survival without such treatment, but no randomized trial addresses this question. If induction treatment is to be used, most centers prefer rabbit polyclonal antisera to OKT3. However, again, no randomized trial has compared the relative efficacy and tolerance of rabbit antisera. Fifty first-heart transplant recipients with standard triple immunosuppression were randomized to receive ATG Fresenius ( n=24) or Thymoglobulin Mérieux ( n=26) as an induction treatment and were followed for 1 year. The two groups were well matched for gender, age, pre-transplant diagnosis and ischemia time. Actuarial survival at 1 year was 87.5% in the Fresenius group and 84.6% in the Mérieux group (Fisher's exact test; P=1). The average number of rejection episodes per patient was comparable in both treatment groups (Fresenius: mean=2.63, SD=1.44; Mérieux: mean=2.46, SD=2.04). Mean time to first rejection was 48.9+/-37.2 days in the Fresenius group versus 59.6+/-54 days in the Mérieux group (Mann-Witney U-test: z=0.77; P=NS). The total number of rejections across all patients was also comparable (Fresenius: 63; Mérieux: 64) as well as the severity of rejection (seven moderate rejections out of a total of 63 in the Fresenius group and eight out of 64 in the Mérieux group). Eighteen Fresenius (75%) and 15 Mérieux (58%) patients suffered from at least one infection ( P=NS). The tolerance to treatment was excellent in both groups. Total lymphocyte count and all subsets of tested lymphocytes decreased rapidly after the introduction of either antiserum but was more pronounced and persisted for longer in the Mérieux group. ATG Fresenius or Thymoglobulin Mérieux as induction treatments in first-heart transplant recipients treated with standard immunosuppression have the same relative efficacy with regard to survival, acute rejection or infection rate, and are well tolerated.