title: Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids.
abstract: Pediatric renal transplant recipients were enrolled in a multicenter, randomized, double-blind trial of steroid withdrawal. Subjects received basiliximab, calcineurin inhibitor, sirolimus and steroids. Of 274 subjects enrolled, 19 (6.9%) subjects developed posttransplant lymphoproliferative disorder (PTLD). The relative hazard (RH) for PTLD was 5.3-fold higher in children aged < or =5 versus those >12 years (p = 0.0017). EBV seronegative subjects had a 4.7-fold higher RH compared to EBV positive subjects (p = 0.02). Among EBV donor+/recipient- (D+/R-) subjects, the RH increased by 6.1-fold (p = 0.0001). In a multivariate model, risk factors included recipient age < or =5 years (RH 3.2, 95% CI: 1.1-9.6, p = 0.034) and EBV D+/R- status (RH 7.7, 95% CI: 1.6-35.9, p = 0.010). Of 19 patients with PTLD, 17 are alive with functioning grafts and 2 lost their grafts, 1 of whom subsequently died of recurrent PTLD. This 'robust' immunosuppression protocol was associated with low rejection rates but an unacceptably high incidence of PTLD. The combination of basiliximab, calcineurin inhibitor, sirolimus and steroids resulted in over-immunosuppression in a high-risk pediatric population and we do not recommend its use. Future studies must include routine viral monitoring to permit early identification of viral activity and a protocol driven reduction of immunosuppression aimed at avoiding complications.
authors.affiliation: University of Washington and Children's Hospital and Regional Medical Center, Seattle, WA, USA. ruth.mcdonald@seattlechildrens.org
authors.forename: R A
authors.initials: RA
authors.lastname: McDonald
authors.forename: J M
authors.initials: JM
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Ho
authors.forename: R
authors.initials: R
authors.lastname: Lindblad
authors.forename: D
authors.initials: D
authors.lastname: Ikle
authors.forename: P
authors.initials: P
authors.lastname: Grimm
authors.forename: R
authors.initials: R
authors.lastname: Wyatt
authors.forename: M
authors.initials: M
authors.lastname: Arar
authors.forename: D
authors.initials: D
authors.lastname: Liereman
authors.forename: N
authors.initials: N
authors.lastname: Bridges
authors.forename: W
authors.initials: W
authors.lastname: Harmon
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000077552:Basiliximab; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000453:epidemiology*; D008297:Male; D015999:Multivariate Analysis; D011183:Postoperative Complications / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D020123:Sirolimus; D016559:Tacrolimus