Induction immunotherapy in pediatric heart transplant recipients: A multicenter study

Robert J. Boucek*, David Naftel, Mark M. Boucek, Richard Chinnock, Robert W. Morrow, Elfriede Pahl, Sharon Disano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Background: The efficacy and safety of induction immunotherapy with antithymocyte antibody preparations (IND) in pediatric heart transplantation is controversial. Experimentally, recipient age is an important determinant of immune 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 rabbit polyclonal antithymocyte serum (N/R-ATS, n = 105) were compared with 255 recipients who did not receive antithymocyte antibodies. The study population were all heart recipients enrolled in the Pediatric Heart Transplant Study 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 group (58/255 and 8/255, respectively) or the OKT3 group (22/101 and 7/101, respectively) with significance of p = 0.001 and 0.06 respectively. Late mortality beyond 30 days after transplant was lowest with N/R-ATS IND compared with the OKT3 and no IND (p = 0.01). Induction did not affect cumulative infections, deaths due to infection, or the frequency of malignancies. Patients excluded from N/R-ATS induction had the highest mortality (18/43), suggesting 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 mortality was 18% for N/R-ATS centers, 21% for OKT3 centers, and 26% for centers not using IND (p = 0.3). The mortalities of recipients < 6 months old at transplant were lowest at centers using N/R-ATS and OKT3 IND compared to centers not using IND (p = 0.04). Cumulative rejection (0.8 vs 1.2 rejection/pt/year, 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 not different from centers not using IND. Conclusion: Following orthotopic transplantation, induction immunotherapy can 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 complications. Since polyclonal anti-T cell antibody preparations appears superior to OKT3 induction in pediatric recipients, the efficacy of ATS induction should be further evaluated in a randomized prospective study in pediatric heart recipients.

Original languageEnglish (US)
Pages (from-to)460-469
Number of pages10
JournalJournal of Heart and Lung Transplantation
Volume18
Issue number5
DOIs
StatePublished - May 1 1999

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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