Incidence of PTLD in Pediatric Renal Transplant Recipients Receiving Basiliximab, Calcineurin Inhibitor, Sirolimus and Steroids

• Published in: American journal of transplantation Vol. 8; no. 5; pp. 984 - 989
• Main Authors: McDonald, R. A., Smith, J. M., Ho, M., Lindblad, R., Ikle, D., Grimm, P., Wyatt, R., Arar, M., Liereman, D., Bridges, N., Harmon, W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2008; Blackwell
• Subjects: Adolescent; Adrenal Cortex Hormones - adverse effects; Adrenal Cortex Hormones - therapeutic use; Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Basiliximab; Biological and medical sciences; Child; Child, Preschool; Cyclosporine - therapeutic use; Double-Blind Method; EBV; Epidemiology; Epstein-Barr virus; Female; General aspects; Hematologic and hematopoietic diseases; Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Infant; Kidney Transplantation - adverse effects; Kidney Transplantation - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoproliferative Disorders - epidemiology; Male; Medical sciences; Multivariate Analysis; pediatric; Postoperative Complications - prevention & control; PTLD; Public health. Hygiene; Public health. Hygiene-occupational medicine; Recombinant Fusion Proteins - adverse effects; Recombinant Fusion Proteins - therapeutic use; renal transplant; Sirolimus - adverse effects; Sirolimus - therapeutic use; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tacrolimus - therapeutic use; Antineoplastic agent; Steroid; Pediatrics; Calcineurin inhibitor; Sirolimus; renal transplant; Hemopathy; Transplantation; Epstein Barr virus; Monoclonal antibody; Homotransplantation; Epidemiology; Kidney; Macrocycle; Incidence; pediatric; Posttransplant lymphoproliferative disorder; Surgery; Immunotherapy; Lymphoproliferative syndrome; EBV; Graft; PTLD; Protein synthesis inhibitor; Child; Gammaherpesvirinae; Human; Corticosteroid; Herpesviridae; Lactone; Macrolide; Infection; Virus; Immunomodulator; Antibiotic; Treatment; Urinary system; Basiliximab; Viral disease; Immunosuppressive agent; Antibacterial agent
• ISSN: 1600-6135; 1600-6143; 1600-6143
• DOI: 10.1111/j.1600-6143.2008.02167.x

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 ≤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 ≤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. Pediatric renal transplant recipients were enrolled in a multi‐center, randomized, double‐blind trial of steroid withdrawal using basiliximab, calcineurin inhibitor, and sirolimus which was terminated due to a high incidence of post‐transplant lymphoproliferative disorder.