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.

Induction Therapy With Thymoglobulin After Heart Transplantation: Impact of Therapy Duration on Lymphocyte Depletion and Recovery, Rejection, and Cytomegalovirus Infection Rates

“…Although the Thymo7 regimen led to more profound and prolonged immunosuppression, the CMV rates within the first year were similar (9% and 5%), as was the rate of in-hospital bacterial infection. The 1-year CMV rates were similar to those reported by Zuckermann et al 13 and lower than those reported by Schnetzler et al 12 The effect of Thymoglobulin on lymphocyte depletion and recovery has only been addressed in one study. 12 This group has demonstrated a similar trend in total lymphocyte count as well as platelets and white blood cells counts.…”

“…The 1-year CMV rates were similar to those reported by Zuckermann et al 13 and lower than those reported by Schnetzler et al 12 The effect of Thymoglobulin on lymphocyte depletion and recovery has only been addressed in one study. 12 This group has demonstrated a similar trend in total lymphocyte count as well as platelets and white blood cells counts. In addition, lymphocyte recovery (Ͼ 1000 per l) in our study occurred earlier, at 6 months, compared with 8 months in the Schnetzler et al study.…”

“…Compared with ATG, Thymoglobulin has been found to have a more pronounced and persistent effect on several subsets of tested lymphocytes. 12 Moreover, a faster lymphocyte recovery (8 weeks vs 8 months) was demonstrated with ATG. We found that Thymo7 resulted in a greater dose-dependent lymphocyte depletion compared with the Thymo5 regimen.…”

“…In addition, lymphocyte recovery (Ͼ 1000 per l) in our study occurred earlier, at 6 months, compared with 8 months in the Schnetzler et al study. 12 The longer lymphocyte depletion is likely attributable to the higher Thymoglobulin dose. Compared with ATG, Thymoglobulin has been found to have a more pronounced and persistent effect on several subsets of tested lymphocytes.…”

Antibody Mediated Rejection of the Cardiac Allograft

“…While ATG has been utilized extensively in heart transplant recipients, no studies have evaluated their use in AMR; rather decreased overall rejection rates have been reported (Renlund et al, 1989;Ladowski et al, 1993;Macdonald et al, 1993;Schnetzler et al, 2002;De Santo et al, 2004). In both induction and rejection protocols, daily infusions are given for as little as 3 to at most 14 days.…”