Role of immunosuppression regimen in post-transplant lymphoproliferative disorder in pediatric heart transplant patients

Background: Post-transplant lymphoproliferative disorder (PTLD) contributes to morbidity and mortality after transplantation. We examined the effect of immunosuppressive regimen on the risk of developing PTLD after pediatric heart transplantation.

Methods: The 324 pediatric heart transplant patients at 2 children's hospitals were retrospectively reviewed for the primary outcome of PTLD development. Patient demographics, rejection frequency, serum cyclosporine and tacrolimus levels, induction therapy, donor and recipient Epstein-Barr virus, and cytomegalovirus serologic status were reviewed and comparisons made between immunosuppressive regimens. Comparisons were also made between transplantation in the early (1984-1995) and late (1996-2008) eras to help account for changes in clinical protocols that occurred during the study period.

Results: PTLD developed in 33 (10%), of whom 109 (34%) were treated with tacrolimus. PTLD developed in 15% of those treated with tacrolimus compared with 8% of patients treated solely with cyclosporine. Tacrolimus use was a significant predictor of PTLD, with a hazard ratio [HR] of 4.04 (95% confidence interval [CI], 2.03-8.02; p = 0.0001). Neither Epstein-Barr virus, cytomegalovirus donor/recipient status, nor gender predicted PTLD development. Younger age at transplant, higher rejection frequency, and induction therapy predicted PTLD development by univariate analysis. Multivariate modeling demonstrated that tacrolimus use (HR, 7.03; 95% CI, 2.87-17.2; p < 0.001) remained an independent predictor of PTLD, when controlling for age, era of transplantation, induction therapy, and rejection frequency.

Conclusions: This study suggests the use of tacrolimus after pediatric heart transplantation is independently associated with an increased risk of PTLD compared with cyclosporine alone.