To induce or not to induce: Do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy?

Robert Higgins, J. K. Kirklin, R. N. Brown, B. K. Rayburn, L. Wagoner, R. Oren, L. Miller, M. Flattery, R. C. Bourge

Research output: Contribution to journalArticle

Abstract

Background: Induction immunosuppression utilizing lymphocytolytic agents in the early peri-operative period has a number of theoretical and practical advantages and disadvantages. However, the efficacy of cytolytic agents as induction therapy remains unproven. Methods: To assess the current impact of induction therapy in heart transplantation, we queried a multi-institutional database regarding the frequency of use, type of agent, duration of therapy and outcomes of 6,553 patients transplanted from 1990 to 2001. A study group of 5,897 patients were identified who survived the first 48 hours post-transplant and received either no induction therapy (n = 4,161) or induction with OKT3 or anti-thymocyte preparations (n = 1,736). Results: By multivariate analysis, risk factors for rejection death were identified and then applied to a model of overall mortality. Among patients with a 1-year risk of rejection death at >5%, induction therapy provided a survival advantage, but survival with induction was decreased when the risk of rejection death was 6 months) support on a ventricular assist device (VAD). Conclusions: Use and application of induction therapy continues to be controversial in heart transplantation. At present, this approach appears to be beneficial in selected patients who are at high risk for rejection death, but likely detrimental in patients who are at low risk for rejection death. Those with a combination of longer term VAD support, of black ethnicity, and having extensive HLA mismatching are most likely to benefit from cytolytic induction therapy.

Original languageEnglish (US)
Pages (from-to)392-400
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume24
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

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Heart-Assist Devices
Heart Transplantation
Therapeutics
Muromonab-CD3
Survival
Thymocytes
Immunosuppression
Multivariate Analysis
Databases
Transplants
Mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Transplantation

Cite this

To induce or not to induce : Do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy? / Higgins, Robert; Kirklin, J. K.; Brown, R. N.; Rayburn, B. K.; Wagoner, L.; Oren, R.; Miller, L.; Flattery, M.; Bourge, R. C.

In: Journal of Heart and Lung Transplantation, Vol. 24, No. 4, 04.2005, p. 392-400.

Research output: Contribution to journalArticle

Higgins, Robert ; Kirklin, J. K. ; Brown, R. N. ; Rayburn, B. K. ; Wagoner, L. ; Oren, R. ; Miller, L. ; Flattery, M. ; Bourge, R. C. / To induce or not to induce : Do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy?. In: Journal of Heart and Lung Transplantation. 2005 ; Vol. 24, No. 4. pp. 392-400.
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abstract = "Background: Induction immunosuppression utilizing lymphocytolytic agents in the early peri-operative period has a number of theoretical and practical advantages and disadvantages. However, the efficacy of cytolytic agents as induction therapy remains unproven. Methods: To assess the current impact of induction therapy in heart transplantation, we queried a multi-institutional database regarding the frequency of use, type of agent, duration of therapy and outcomes of 6,553 patients transplanted from 1990 to 2001. A study group of 5,897 patients were identified who survived the first 48 hours post-transplant and received either no induction therapy (n = 4,161) or induction with OKT3 or anti-thymocyte preparations (n = 1,736). Results: By multivariate analysis, risk factors for rejection death were identified and then applied to a model of overall mortality. Among patients with a 1-year risk of rejection death at >5{\%}, induction therapy provided a survival advantage, but survival with induction was decreased when the risk of rejection death was 6 months) support on a ventricular assist device (VAD). Conclusions: Use and application of induction therapy continues to be controversial in heart transplantation. At present, this approach appears to be beneficial in selected patients who are at high risk for rejection death, but likely detrimental in patients who are at low risk for rejection death. Those with a combination of longer term VAD support, of black ethnicity, and having extensive HLA mismatching are most likely to benefit from cytolytic induction therapy.",
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