Role for immune monitoring to tailor induction prophylaxis in pediatric heart recipients

Abstract

Tailoring rATG induction with CD3 monitoring results in less infection, reduced costs, and similar rejection. Retrospective review of HTx recipients receiving rATG induction. Control cases received "usual" rATG dosing (1.5 mg/kg/day typically × 5 days). Starting in October 2009, absolute CD3 monitoring (target <25 cells/mm(3) ) guided rATG dosing (study cases). Outcomes included first-year incidence of infection/rejection, direct costs of therapy, and incidence of PTLD/death. Study cases (n = 32) received fewer doses of rATG (median 4 vs. 5, p < 0.001) and less total rATG (median 3.2 vs. 7.4 mg/kg, p < 0.001) compared with controls (n = 17). There was no difference in incidence of infection, rejection, or patient survival during the first year post-HTx. There was one early death in both groups and one late case of PTLD in the control group. Drug savings were significant (median drug cost per patient $2718 vs. $4756, p < 0.001). CD3-tailored rATG induction in HTx recipients is associated with reduced drug costs and similar rates of rejection/infection. Longer follow-up will determine whether extended benefits are associated with this induction monitoring strategy.

Clinical approach to acute cellular rejection from the pediatric heart transplant society

“…can be used to guide dosing or duration. 15 3. Slower infusion rates can mitigate hemodynamic instability, pyrexia or other side effects.…”

“…There are many dosing considerations for rATG: Trend daily cell counts. Dose reduction is indicated for severe thrombocytopenia. Lymphocyte count and T/B cell subsets (goal CD3 < 25 cells/μl) can be used to guide dosing or duration 15 Slower infusion rates can mitigate hemodynamic instability, pyrexia or other side effects. If simultaneously treating AMR, give rATG immediately after plasmapheresis and try to allow ≥12 h between ATG and plasmapheresis to limit ATG removal.…”

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

“…Where this approach is applied, the ISHLT guidelines advise targeting a CD3 count in the range 25–50 cells/mm 3 or an absolute total lymphocyte count <100–200 cells/mm 3 [ 20 ]. Data on immune monitoring in pHTx are scant but a retrospective study compared CD3-guided rATG dosing in 32 patients versus 17 historical controls given fixed rATG dosing (1.5 mg/kg, usually for 5 days) [ 65 ]. The patient group managed with CD3 monitoring received a significantly lower total rATG dose (median 3.2 versus 7.4 mg/kg, p<0.001), with no difference in rates of rejection, patient survival, or infection.…”

Retransplantation of the Pediatric Heart Recipient

“…If postoperative bleeding is significant and induction therapy with anti-thymocyte antibodies (ATG) was deployed, the patient should be evaluated for the development of ATG-induced thrombocytopenia. Utilizing T-cell number-directed dosing (CD3 count) may reduce the total dose of ATG given and thus the incidence of ATG-induced thrombocytopenia (Uber et al 2004;Thrush et al 2014). Induction with basiliximab is also an option; however, this decision should be made prior to transplantation as basiliximab is designed for the first dose to be given 2 h prior to the operation (Vincenti et al 2003).…”