OKT3 treatment in refractory pediatric heart transplant rejection.
BACKGROUND
The anti-lymphocyte monoclonal antibody OKT3 has been shown to be effective in the management of steroid-resistant and/or fulminant heart transplant rejection in adults. In addition, some studies suggest that OKT3 may have a role in the management of transplant coronary artery disease (TxCAD). To date, there are limited data regarding the use of OKT3 treatment of refractory rejection or graft failure in children. Our study examines OKT3 treatment in steroid-resistant rejection, rejection with hemodynamic compromise, and TxCAD in children.


METHODS
Thirty-eight patients received 53 courses of OKT3 for treatment of rejection and/or graft dysfunction. Primary indications for OKT3 were steroid-resistant rejection (n = 27), rejection with hemodynamic compromise (n = 22), and TxCAD (n = 4). Resolution of rejection was considered absence of biopsy-proven rejection (< grade 2) or resolved TxCAD.


RESULTS
OKT3 use in steroid-resistant rejection was associated with a lower incidence of rejection in the 3 months after OKT3 than 3 months before OKT3, median rejection episodes of 2.5 vs 0, p < 0.0001. In rejection with hemodynamic compromise, 20 subjects (91%) demonstrated improved hemodynamics after OKT3 and survived to hospital discharge. The use of OKT3 treatment for TxCAD failed to demonstrate resolution or improvement in angiographic TxCAD in any subject. Only 5 OKT3 treatment courses were stopped secondary to severe adverse side effects.


CONCLUSIONS
OKT3 treatment in refractory pediatric heart transplant rejection is efficacious in acute rejection. OKT3 management in pediatric TxCAD is less clear, with no proven benefit identified in this study. OKT3 use in pediatric refractory heart rejection has significant side effects, but is tolerable and safe with close monitoring.
Wilmot
Ivan
I
Egleston Children's Hospital, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Kanter
Kirk R
KR
Vincent
Robert N
RN
Berg
Alexandria M
AM
Mahle
William T
WT
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000601:surgery; D006084:Graft Rejection / Q000188:drug therapy* / Q000503:physiopathology; D016027:Heart Transplantation / Q000276:immunology; D006439:Hemodynamics; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012189:Retrospective Studies
D007166:Immunosuppressive Agents; D016853:Muromonab-CD3