title: Persistent donor-specific alloreactivity may portend delayed liver rejection during drug minimization in children.
abstract: Immunoreactivity, immunosuppression requirement and liver graft function was assessed serially for its relationship to delayed/recurrent acute cellular rejection (ACR) after the first 60 days in 36 pediatric primary liver transplant (LTx) recipients. Subjects were classified as rejectors (n=20) or Non-Rejectors (n=16) based on the presence/absence of biopsy-proven ACR in the first 60 days. All children received anti-lymphocyte induction and steroid-free Tacrolimus or Sirolimus monotherapy, as reported previously. Median age was 4 years (0.45-18) and follow-up was 570 days (106-1144). Compared with non-rejectors, rejectors 1. took significantly longer to achieve reduced donor-specific alloreactivity by MLR (p=0.049), and "low" TAC/SRL whole blood requirements defined as TAC levels < or = 8 ng/ml (p=0.0048), 2. experienced significantly greater variation in time to achieve reduced donor-specific immunoreactivity (SEM 0.8 vs 3.85, p=0.0048), and 3. experienced greater ACR incidence during minimization of immunosuppression (35% versus 6%, p=0.032). Serial monitoring of immunoreactivity may increase the safety with which immunosuppression is minimized in pediatric LTx.
authors.affiliation: University of Pittsburgh, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15217, USA.
authors.forename: Nandita
authors.initials: N
authors.lastname: Khera
authors.forename: Janine
authors.initials: J
authors.lastname: Janosky
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: George
authors.initials: G
authors.lastname: Mazariegos
authors.forename: Amadeo
authors.initials: A
authors.lastname: Marcos
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sindhi
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D015994:Incidence; D007223:Infant; D016031:Liver Transplantation; D007959:Lymphocyte Culture Test, Mixed; D012008:Recurrence; D020123:Sirolimus / Q000097:blood / Q000627:therapeutic use; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus