Initial data on basiliximab in critically ill children undergoing heart transplantation.
BACKGROUND
More children are coming to heart transplantation on extracorporeal membrane oxygenation (ECMO), or inotropic support and/or with renal impairment. The use of basiliximab, a chimeric monoclonal antibody against CD25 (interleukin 2 receptor alfa) has not been previously reported in critically ill pediatric heart transplant recipients. Basiliximab has potential advantages in the treatment of patients with renal impairment.


METHODS
Basiliximab was provided to 29 patients (median age 7.8 years; range 0.4-16 years) on ECMO, with renal impairment or receiving intravenous inotropes at transplantation. Children normally received 2 doses on Day 0 and Day 4 after transplantation. Calcineurin inhibitor was provided in low dose or withheld altogether in patients with renal impairment. Flow cytometry was used to monitor CD25.


RESULTS
At transplantation, 11 patients were prescribed cyclosporine; the remaining 18 received tacrolimus. All but 4 patients had subtherapeutic levels of calcineurin inhibitor in the first postoperative week. Excluding these 4, there were 19 patients who had more than 4 consecutive doses of calcineurin inhibitor canceled in the first week (median 8 doses; range 3-40 doses). A total of 71 surveillance biopsies were performed, and 4 episodes of severe acute rejection occurred in the first 6 months. In all but one child, the glomerular filtration rate had returned to, or improved on baseline measurement by 1 month after transplantation. Infections rates were low and acceptable. CD25 was undetectable at first assessment, and in all but 1 patient (on ECMO) for at least 2 to 3 weeks thereafter. There were no adverse effects.


CONCLUSIONS
Basiliximab was well tolerated in this group of very ill children. In children with pre- or postoperative renal dysfunction, where doses of calcineurin inhibitor were low or canceled, basiliximab was associated with a low incidence of rejection. Posttransplant ECMO may reduce the efficacy of basiliximab. These preliminary results are encouraging and now need confirmation in a large, randomized trial.
Ford
Katrina A
KA
Pharmacy Department, Great Ormond Street Hospital for Children, London, United Kingdom. fordk2@gosh.nhs.uk
Cale
Catherine M
CM
Rees
Philip G
PG
Elliott
Martin J
MJ
Burch
Michael
M
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000077552:Basiliximab; D019703:Calcineurin / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications; D008297:Male; D010750:Phosphoproteins / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000097:blood; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; C491861:CABIN1 protein, human; D007166:Immunosuppressive Agents; D010750:Phosphoproteins; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D019703:Calcineurin; D016559:Tacrolimus