Monitoring and Risk-Based Therapeutic Strategy Eliminates Posttransplant Lymphoproliferative Disease

Bryan DeBusk, PhD

July 11, 2008

July 11, 2008 (Paris, France) — The retrospective evaluation of a preventative and preemptive intervention for pediatric recipients of liver transplants has shown that a combination of prophylactic ganciclovir and regular monitoring for Epstein-Barr virus (EBV) effectively eliminates posttransplant lymphoproliferative disease (PTLD).

Robert Venick, MD, assistant clinical professor of pediatric gastroenterology, hepatology, and nutrition at the University of California at Los Angeles' Mattel Children's Hospital, presented the results of the study here at the 2008 Joint International Congress of ILTS, ELITA & LICAGE.

"Prior to the late '90s, the incidence of PTLD following pediatric liver transplantation was reported as 5% to 15%," Dr. Venick told Medscape Transplantation. "In an effort to reduce the incidence of PTLD and improve patient outcomes, a preventative and preemptive monitoring and therapeutic approach was instituted at our institution beginning in 1998."

Starting in January 1998, pediatric patients receiving liver transplants were assigned PTLD-prevention strategies on the basis of risk. Patients under 12 months of age and patients who tested negative for EBV were categorized as high risk and intravenously administered 6 to 10 mg/kg ganciclovir per day for 100 days, plus oral acyclovir 40 mg/kg per day for 2 years. Low-risk patients were intravenously administered 6 to 10 mg/kg ganciclovir per day for 4 weeks, plus daily oral acyclovir 40 mg/kg for 2 years. All patients received polymerase chain reaction (PCR) testing for serum EBV levels every 1 to 2 months. Physicians reduced immunosuppression and provided a course of intravenous ganciclovir for patients with persistent moderately positive (100–500 copies of viral DNA per test) or strongly positive (>500 copies of viral DNA per test) viremia episodes.

Dr. Venick and his colleagues identified 192 pediatric patients (median age, 21 months) who received liver transplants and more than 6 months of follow-up (median follow-up time, 70 months) at their center between January 1998 and June 2007. Physicians categorized 48% of the recipients as high risk. EBV PCR testing identified viremia episodes in 37% of recipients, with a mean time to viremia of 4.4 ± 3.7 months after transplant and peak virus loads at a mean of 10.0 ± 5.9 months. During 1007 patient-years of follow-up, patients received treatments according to the preventative and preemptive monitoring and therapy protocol; fewer-than-expected strongly positive viremia episodes (n = 12) and no cases of PTLD occurred.

Anil Dhawan, MD, moderator of the session and professor of pediatric hepatology at King's College Hospital in London, United Kingdom, told Medscape Transplantation that other centers are likely to adopt the strategies outlined by Dr. Venick. "They have been able to reduce the incidence of this dreadful complication in children with liver transplantation 10-fold — the best in the world," Dr. Dhawan remarked.

Dr. Venick agreed that the results hold considerable promise for eliminating PTLD. "The consequences of PTLD in this patient population are grave, with mortality rates between 10% and 35%," Dr. Venick explained. "Through the use of this protocol, which relies on the risk stratification of individual patients, close monitoring of quantitative EBV PCRs, antiviral medication for the first 2 years posttransplant, and immunosuppression minimization, we have had 0 cases of PTLD in over 1000 patient-years of follow-up."

The study did not receive commercial support. Drs. Venick and Dhawan have disclosed no relevant financial relationships.

2008 Joint International Congress of ILTS, ELITA & LICAGE: Abstract 515. Presented July 10, 2008.

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