Induction immunotherapy in pediatric heart transplant recipients: A multicenter study

Background: The efficacy and safety of induction immunotherapy with antithy mocyte antibody preparations (IND) in pediatric heart transplantation is co ntroversial. Experimentally, recipient age is an important determinant of i mmune responses. The effects on induction immunotherapy were determined by an analysis of outcomes of 465 pediatric (age < 18 years) heart recipients that either did or did not receive IND in the first week post-transplant. Methods: The outcomes of 2 groups who received either OKT3 (n = 101) or rab bit polyclonal antithymocyte serum (N/R-ATS, n = 105) were compared with 25 5 recipients who did not receive antithymocyte antibodies. The study popula tion were all heart recipients enrolled in the Pediatric Heart Transplant S tudy Group (PHTS) between January 1993 and December 1995 and followed up to 36 months. Results: Overall mortality and death due to rejection were lowest with N/R- ATS IND (8/105 and 1/105, respectively) compared with the no-induction grou p (58/255 and 8/255, respectively) or the OKT3 group (22/101 and 7/101, res pectively) with significance of p = 0.001 and 0.06 respectively. Late morta lity beyond 30 days after transplant was lowest with N/R-ATS IND compared w ith the OKT3 and no IND CF, = 0.01). Induction did not affect cumulative in fections, deaths due to infection, or the frequency of malignancies. Patien ts excluded from N/R-ATS induction had the highest mortality (18/43), sugge sting that the protocol's exclusion criteria identified a high-risk group. To minimize potential effect(s) of exclusion bias, patients transplanted at centers participating in the N/R-ATS induction trial were reanalyzed with a post hoc intent-to-treat analysis assigning patients by center (IND or no IND) irrespective of actual treatment. With this analysis overall mortalit y was 18% for N/R ATS centers, 21% for OKT3 centers, and 26% for centers no t using IND (p = 0.3). The mortalities of recipients < 6 months old at tran splant were lowest at centers using N/R-ATS and OKT3 IND compared to center s not using IND (p = 0.04). Cumulative rejection (0.8 vs 1.2 rejection/pt/y ear, p = 0.01) and freedom from rejection death (99% vs 93% at year 1, p = 0.02) of the N/R-ATS centers were lower compared to OKT3 centers but were n ot different from centers not using IND. Conclusion: Following orthotopic transplantation, induction immunotherapy c an exert the enduring benefit of reducing late deaths, a possible surrogate for rejection severity, in recipients less than 6 months of age, while not being associated with higher rates of infectious or malignant complication s. Since polyclonal anti-T cell antibody preparations appears superior to O KT3 induction in pediatric recipients, the efficacy of ATS induction should be further evaluated in a randomized prospective study in pediatric heart recipients.