Sirolimus-Based Immunosuppression Is Associated with Decreased Incidence of Post-Transplant Lymphoproliferative Disorder after Heart Transplantation: A Double-Center Study

Rabea Asleh, Darko Vucicevic, Tanya M. Petterson, Walter K. Kremers, Naveen L. Pereira, Richard C. Daly, Brooks S. Edwards, D. Eric Steidley, Robert L. Scott, Sudhir S. Kushwaha

Research output: Contribution to journalArticlepeer-review

Abstract

Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce proliferation of lymphoid cells; thus, their use for immunosuppression after heart transplantation (HT) may reduce post-transplant lymphoproliferative disorder (PTLD) risk. This study sought to investigate whether the sirolimus (SRL)-based immunosuppression regimen is associated with a decreased risk of PTLD compared with the calcineurin inhibitor (CNI)-based regimen in HT recipients. We retrospectively analyzed 590 patients who received HTs at two large institutions between 1 June 1988 and 31 December 2014. Cox proportional-hazard modeling was used to examine the association between type of primary immunosuppression and PTLD after adjustment for potential confounders, including Epstein–Barr virus (EBV) status, type of induction therapy, and rejection. Conversion from CNI to SRL as primary immunosuppression occurred in 249 patients (42.2%). During a median follow-up of 6.3 years, 30 patients developed PTLD (5.1%). In a univariate analysis, EBV mismatch was strongly associated with increased risk of PTLD (HR 10.0, 95% CI: 3.8–26.6; p < 0.001), and conversion to SRL was found to be protective against development of PTLD (HR 0.19, 95% CI: 0.04–0.80; p = 0.02). In a multivariable model and after adjusting for EBV mismatch, conversion to SRL remained protective against risk of PTLD compared with continued CNI use (HR 0.12, 95% CI: 0.03–0.55; p = 0.006). In conclusion, SRL-based immunosuppression is associated with lower incidence of PTLD after HT. These findings provide evidence of a benefit from conversion to SRL as maintenance therapy for mitigating the risk of PTLD, particularly among patients at high PTLD risk.

Original languageEnglish (US)
Article number322
JournalJournal of Clinical Medicine
Volume11
Issue number2
DOIs
StatePublished - Jan 1 2022

Keywords

  • Heart trans-plantation
  • Immunosuppression
  • MTOR inhibitors
  • Post-transplant lymphoproliferative disorder
  • Sirolimus

ASJC Scopus subject areas

  • General Medicine

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