A study in the January 18 issue of JAMA reveals that the majority of children who received liver transplant grafts from a parent were able to stay off immunosuppression therapy for at least 1 year with normal graft function after gradual withdrawal from the therapy.
Individuals who receive a solid organ transplantation commonly experience lifelong immunosuppression with several associated toxic effects, including opportunistic infection, malignancy, and renal dysfunction.
The researchers explain:
"However, in liver transplantation, several single-center experiences suggest that a proportion of liver recipients can maintain normal allograft function without immunosuppression, termed operational tolerance.
Based on these studies, the estimated frequency of operational tolerance has been proposed to be as high at 20 percent. Although withdrawal of immunosuppression therapy in liver allograft recipients can precipitate rejection, most episodes are reversible without long-term consequences, rendering this patient population appropriate for drug minimization, discontinuation, or both."
In order to analyze the feasibility of withdrawal of immunosuppression therapy in children who receive liver transplants, Sandy Feng, M.D., Ph.D., of the University of California, San Francisco, and her team conducted a trial involving 20 children who received living donor liver transplants from a parent for diseases other than viral hepatitis or an autoimmune disease who underwent immunosuppression withdrawal.
The median age of recipients at transplantation was 6.9 months and 8 years 6 months at enrollment. All participants were white and 55% (11) were male. Participants were followed up for a median of 32.9 months.
Enrollment criteria included stable allograft function while taking a single immunosuppressive medication as well as no evidence of acute or chronic rejection or significant fibrosis (development of excess fibrous connective tissue) on liver biopsy.
Between June 2006 and November 2009, gradual immunosuppression withdrawal occurred over a minimum of 36 weeks. The primary end point was defined as participants who stayed off immunosuppression therapy for at least one year with normal graft function.
60% (12 of the 20 participants) stayed off the therapy for at least one year and were defined as tolerant while the other 8 participants were termed non-tolerant. Of the 8 participants termed non-tolerant, 3 did not meet the primary end point after immunosuppression withdrawal and 5 did not meet the primary end point during withdrawal.
The 12 tolerant participants were off therapy for a median of 35.7 months, while the median time to not meeting the primary outcome measure was 5.7 months after initiation of withdrawal.
4 of the non-tolerant participants developed allograft dysfunction a median of 121.5 days after initiating immunosuppression withdrawal. 1 participant was diagnosed by liver biopsy as having moderate acute rejection, while 3 were diagnosed with indeterminate or borderline acute rejection.
Tolerant patients began immunosuppression withdrawal later after transplantation (median 100.6 months) than non-tolerant patients (73.0 months).
7 participants received treatment with increased reinitiation of immunosuppression therapy; all returned to baseline allograft function. The researchers observed no deaths, opportunistic infections of graft loss.
The researchers explain:
"These outcomes demonstrate that immunosuppression withdrawal in this clinical trial setting appears to be feasible for both tolerant and non-tolerant patients.
Our surprising finding that an unexpectedly high proportion of well-defined pediatric cohort are operationally tolerant with stable allograft function and histology sets that agenda for larger studies with longer follow-up to define the frequency, assess the durability, and derive a predictive profile of operational tolerance for pediatric liver transplant recipients."
Written by Grace Rattue