Antiviral prophylaxis for the prevention of post-transplantation lymphoproliferative disorder

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Abstract

BACKGROUND

Does Epstein-Barr virus (EBV) prophylaxis lower the risk of post-transplantation lymphoproliferative disorder (PTLD)? Investigations conducted to date, often involving small populations or historical controls, have yielded conflicting results.

OBJECTIVE

To evaluate, in a multicenter case-control study, the efficacy of antivirals in preventing development of PTLD in renal transplant recipients.

DESIGN AND INTERVENTION

Data from patients who underwent kidney-only transplantation during or after July 1995 and developed PTLD in 2001 were obtained from centers belonging to the United Network for Organ Sharing (UNOS) and from UNOS records. Each patient was matched with a maximum of four controls from the same center and the same age-group (≤18 years or >18 years), who were alive for at least as long as the patient between transplantation and PTLD development, but who had no clinical signs of PTLD. Controls had received their transplant within 1 month of the patient (for those aged >18 years), or within 6 months (for those aged ≤18 years). Information on demographics, rejection history, antiviral use and viral status was collected from patients' records. Use of antivirals beginning after transplantation and ≥30 days before diagnosis of PTLD (or during a similar interval for controls) was recorded; therapy that began within 21 days of transplantation was designated prophylactic unless otherwise stated. Conditional logistic regression analysis was employed to analyze the influence of antivirals on the risk of PTLD.

OUTCOME MEASURE

The endpoint was PTLD.

RESULTS

The analysis included 100 patients with biopsy-proven PTLD, and 375 controls. Pretransplantation EBV status was available for 58% of patients overall, of whom 75% were seropositive. The risk of developing PTLD was considerably higher in EBV-negative than EBV-positive patients (age-adjusted odds ratio [OR] 5.5; 95% CI 2.5-11.7). Use of antivirals (overall prevalence 65%) was associated with an unadjusted OR for developing PTLD of 0.56 (95% CI 0.35-0.86); the individual unadjusted ORs for aciclovir and ganciclovir alone were 0.61 (95% CI 0.36-1.05) and 0.47 (95% CI 0.25-0.87). In the multivariate regression analysis, the risk of developing PTLD with aciclovir or ganciclovir prophylaxis was even lower (ORs 0.46, 95% CI 0.14-1.52 and 0.17, 95% CI 0.05-0.56, respectively). EBV seronegativity and history of rejection were associated with increased risks of PTLD (ORs 12.58, 95% CI 3.51-45.06 and 2.51, 95% CI 0.98-6.44, respectively). When EBV-negative patients were excluded from the analysis, the risk of PTLD remained lower for those given ganciclovir (OR 0.28, 95% CI 0.08-0.96) but was not significantly reduced in aciclovir-treated patients. For every 30 days of treatment, ganciclovir, but not aciclovir, was associated with a considerable (−38%) reduction in the adjusted risk of developing PTLD in the first year after transplantation.

CONCLUSION

Renal transplant recipients and donors should be screened for EBV; antiviral prophylaxis is indicated for those at high risk of PTLD.

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