A Proposal for Early Dosing Regimens in Heart Transplant Patients Receiving Thymoglobulin and Calcineurin Inhibition

Abstract

There is currently no consensus regarding the dose or duration of rabbit antithymocyte globulin (rATG) induction in different types of heart transplant patients, or the timing and intensity of initial calcineurin inhibitor (CNI) therapy in rATG-treated individuals. Based on limited data and personal experience, the authors propose an approach to rATG dosing and initial CNI administration. Usually rATG is initiated immediately after exclusion of primary graft failure, although intraoperative initiation may be appropriate in specific cases. A total rATG dose of 4.5 to 7.5 mg/kg is advisable, tailored within that range according to immunologic risk and adjusted according to immune monitoring. Lower doses (eg, 3.0 mg/kg) of rATG can be used in patients at low immunological risk, or 1.5 to 2.5 mg/kg for patients with infection on mechanical circulatory support. The timing of CNI introduction is dictated by renal recovery, varying between day 3 and day 0 after heart transplantation, and the initial target exposure is influenced by immunological risk and presence of infection. Rabbit antithymocyte globulin and CNI dosing should not overlap except in high-risk cases. There is a clear need for more studies to define the optimal dosing regimens for rATG and early CNI exposure according to risk profile in heart transplantation.

A Review of Induction with Rabbit Antithymocyte Globulin in Pediatric Heart Transplant Recipients

“…Our group recently published a review that concluded, based on 2 published studies [ 33 , 61 ], that a maximum total rATG dose of 7.5 mg/kg is adequate in children at standard immunological risk receiving CNI-based maintenance therapy [ 13 ]. A lower cumulative dose (but not less than 3.5 mg/kg) may be sufficient in younger, lower-risk patients who are receiving CNI therapy, in view of the increased risk for PTLD in the youngest recipients [ 8 , 13 ], although this has not been assessed clinically. The duration of rATG infusion should not be less than 6 h [ 13 ].…”

“…A lower cumulative dose (but not less than 3.5 mg/kg) may be sufficient in younger, lower-risk patients who are receiving CNI therapy, in view of the increased risk for PTLD in the youngest recipients [ 8 , 13 ], although this has not been assessed clinically. The duration of rATG infusion should not be less than 6 h [ 13 ].…”

“…The authors of the present study all represent German-speaking HTx centers experienced in the use of rATG induction. Our group has previously published expert opinion articles concerning the appropriate use of rATG induction in adults undergoing HTx [ 8 ] and proposals for rATG dosing and early maintenance regimens in this setting [ 13 ]. Recognizing the important differences between adult HTx and pHTx and attempts towards patient-orientated tailored immunosuppressive regimens, we aimed to review available studies relating to rATG induction in pHTx, and to consider its role within modern immunosuppressive strategies in this unique population.…”

Renal protection strategies after heart transplantation

“…The immunological risk and the presence of infection influence the initial CNI target levels. ATG and CNIs should not overlap except in high‐risk cases …”

“…ATG and CNIs should not overlap except in high-risk cases. 26 Anti-IL2 RA allows a delayed start of CNIs after HTx with a lower rate of renal failure and without an increased risk of acute rejection. 27 Delgado et al 28 compared HTx patients who received ATG or anti-IL2 RA induction (both with delayed CsA).…”