Initial experience with CNI-free immunosuppression in pediatric heart transplant recipients - anticipating PTLD and chronic renal insufficiency

Introduction: Posttransplant lymphoproliferative disorder (PTLD) and renal impairment are major complications in the long-term follow-up after pediatric heart transplantation (ped. HTx). Their severity is related to the degree of immunosuppression (IS) and especially to the exposure to calcineurin inhibitors (CNI). For that reason a CNI-free regimens utilizing proliferation signal inhibitors (PSI) was developed for selected patients; however, their effectiveness remains unclear. This work presents the initial experience with a CNI-free IS in ped. HTx recipients.

Method: Of the 186 maintenance patients 6 were changed to a CNI-free, PSI-based (MMF + Everolimus), protocol during 2009-2013. Inclusion criteria were absence of acute rejection during the last 2 years, current biopsy and exclusion of significant cardiac allograft vasculopathy by angio and histology. Target blood levels for everolimus were 5-8 ng/ml and for MMF 2.0-4 ng/ml. Rejection was excluded non-invasively and with follow-up biopsy.

Results: Median posttransplant time was 10.2 (6.2 - 11.7) and follow-up time 1.4 (0.6 - 5.1) years. Acute rejection rate was 0%. Renal function stabilized and PTLD/relapse did not occur in 4/6 patients, although viral load was increased in the majority of patients. Two patients received CD20-antibodies due to suspected relapse of PTLD, which was not confirmed by histology.

Conclusions: Individual IS should be considered for each patient during the posttransplant follow-up. CNI-free and PSI-based IS might be feasible in patients with signs of PTLD or chronic renal insufficiency. Multi-center studies are urgently needed to evaluate and confirm effectiveness and safety of this “off-label” IS-protocol.