Biopsy-proven acute rejection during immunosuppression withdrawal reversible in children

BOSTON — Among pediatric liver transplant recipients, biopsy-proven acute rejection during protocolized and supervised immunosuppression withdrawal was reversed with steroids and tacrolimus.

The NIH-funded, prospective, multicenter iWITH trial was conducted to determine the efficacy and safety of immunosuppression withdrawal in pediatric liver transplant patients at 12 pediatric transplant centers in North America.

“Our aim is to describe the characteristics of biopsy proven acute rejection during highly supervised immunosuppression withdrawal, and these characteristics include the timing of rejection, the histologic severity and the clinical severity,” Veena L. Venkat, MD, from the department of pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, said at The Liver Meeting.

Veena L. Venkat

The study included 74 pediatric liver transplant recipients (42% boys, 31% living donor recipients; 59% biliary atresia) who initiated immunosuppression withdrawal between September 2012 and March 2014. Patients were aged younger than 6 years at transplantation and were at least 4 years post-transplant at the time of immunosuppression withdrawal. Alanine aminotransferase (ALT) and gamma-glutamyl-transferase (GGT) were less than 50 IU/mL. All patients were on calcineurin inhibitor monotherapy at the time of initiation.

Immunosuppression withdrawal occurred gradually in eight steps over 36 to 48 weeks. At each site, biopsy proven acute rejection was treated according to standard of care.

At the end of March 2014, 42% of patients were off immunosuppression for a median of 12 weeks (range, 0.7-39.9), 31% remained on immunosuppression withdrawal and 27% had biopsy proven acute rejection.

Of the 20 biopsy proven acute rejection episodes, 15 occurred at less than 33% of the tacrolimus dose before immunosuppression withdrawal; 14 were scored as mild, five as moderate and one as inadequate based on Banff criteria. The median rejection activity index was 4 (range, 3-6). In addition to tacrolimus, 16 of those patients received oral corticosteroids, and four received IV plus oral corticosteroids. ALT and GGT levels were less than 50 IU/L in 45% of patients after 4 weeks, and in 90% of patients by 16 weeks after biopsy proven acute rejection.

“By 44 weeks, all but one [patient] … had resolved rejection” Venkat said. “These data suggest that highly structured and supervised immunosuppression withdrawal is safe in the short term for selected pediatric liver transplant recipients. Ongoing follow up is required to assess the long-term safety and impact of failed [immunosuppression withdrawal].” – by Adam Leitenberger

For more information:

Venkat VL. Abstract 1. Presented at: The Liver Meeting ; Nov. 7-11, 2014; Boston.

Disclosure: Venkat reports no relevant financial disclosures. See the abstract for the other researchers’ relevant financial disclosures.