Claire Beguin

Early signs and risk factors for the increased incidence of Epstein-Barr virus-related posttransplant lymphoproliferative diseases in pediatric liver transplant recipients treated with tacrolimus.

BACKGROUND Posttransplant lymphoproliferative disease (PTLD) is a life-threatening condition the incidence of which in pediatric solid organ transplantation may be related to the immunosuppressive load. It has been suggested that tacrolimus, a new and potent immunosuppressor, causes an increased incidence of this syndrome. METHODS The incidence, early signs, and risk factors for lymphoproliferative disease were reviewed in a cohort of 89 pediatric liver transplant recipients treated with tacrolimus. RESULTS Eighteen patients (20%) developed a PTLD-16 concomitant to a primary Epstein-Barr virus (EBV) infection and 2 with previous immunity against EBV. Three additional patients had preliminary signs of PTLD concomitant to primary EBV infection, but did not develop individualized lymphoid masses. Six patients died (6.7% of all tacrolimus-treated patients). Mean tacrolimus blood level during the 3 months preceding EBV infection reached 11.8+/-1.8 ng/ml in PTLD patients versus 9.4+/-3.4 ng/ml in non-PTLD patients (0.05<P<0.1). Previous OKT3 or antithymocyte globulin treatment was also significantly associated to PTLD. There was no association with age, rejection episodes, steroid-resistant rejection, prior cytomegalovirus infection, HLA mismatch, living donor or cadaveric organ transplantation, United Network for Organ Sharing status at the time of orthotopic liver transplant, and primary or rescue tacrolimus treatment. A significant increase of total gamma-globulin level occurred in PTLD patients, and mono/oligoclonal production was significantly associated to PTLD. CONCLUSION In EBV-infected pediatric liver transplant recipients, use of OKT3 or antithymocyte globulin and high tacrolimus blood levels are risk factors for a significant increase in the incidence of PTLD. An increase in total gamma-globulin level and appearance of mono/oligoclonal immunoglobulin production are the major preliminary signs of the syndrome.

Steroid-free, tacrolimus-basiliximab immunosuppression in pediatric liver transplantation: Clinical and pharmacoeconomic study in 50 children†

Corticosteroid‐free immunosuppression (IS) may be potentially beneficial for transplanted patients, particularly children. The purpose of this study was to evaluate the efficacy and cost of such strategy in primary pediatric liver transplantation (LT). Fifty pediatric LT recipients were prospectively treated with a steroid‐free, tacrolimus‐basiliximab–based IS (group TB). A group of 34 children transplanted under a conventional tacrolimus‐steroids regimen served as control series (group TS). Groups TB and TS were compared regarding patient and graft survival, rejection incidence, infectious complications, and growth, as well as cost of the transplant procedure. Patient and graft survivals at 3 years were 96% and 94% in group TB, versus 91% and 88% in group TS (P = 0.380 and P = 0.370, respectively). Rejection‐free graft survival at 3 years was 72% in group TB, versus 41% in group TS (P = 0.007). Patients in group TB had significantly less viral infections than patients in group TS (P = 0.045). Height standard deviation score was significantly enhanced in children from group TB, when compared to group TS. Medical care costs were similar in both groups. Steroid avoidance together with basiliximab immunoprophylaxis was not harmful in terms of allograft acceptance, and even seemed to be beneficial in the long term. Liver Transpl, 2008.

Prevalence and determinants of coronary and aortic calcifications assessed by chest CT in renal transplant recipients.

Background: Coronary artery calcifications independently predict cardiovascular events (CVE) in the general population. We assessed the prevalence and determinants of coronary (CAC) and thoracic aorta (AoC) calcifications in renal transplant recipients (RTR). Methods: Consecutive RTR living in Belgium, with an isolated kidney graft functioning for more than 1 year, were asked to participate. They underwent a 16-slice spiral computerized tomography in order to measure calcium mass. Demographic, clinical, biochemical and urinary parameters were recorded. Results: We included 281 patients. CAC and AoC were detected in 81 and 85%, with geometric means (SD) of 52.2 (4.9) and 99.3 (8.2) mg, respectively. By multiple linear regression, independent predictors of both types of calcifications included older age, longer time on dialysis, a history of CVE, of multiple transplantations and of smoking. Other determinants of CAC were male gender, current statin use and history of parathyroidectomy, and other determinants of AoC included higher pulse pressure, shorter time under mycophenolate mofetil and current use of anti-vitamin-K. Conclusion: The prevalence of both CAC and AoC is substantial in RTR. We delineate independent determinants either common to both CAC and AoC or specific to one, and known as classic or chronic kidney disease related risk factors.