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Long-term management of immunosuppression after pediatric liver transplantation: is minimization or withdrawal desirable or possible or both?

ABSTRACT: PURPOSE OF REVIEW:The aim is to review available data regarding the risks and benefits of indefinite immunosuppression against attempted immunosuppression withdrawal for children who have undergone liver transplantation. RECENT FINDINGS:Emerging data suggest that conventional immunosuppression practices may well be responsible for a substantial proportion of the long-term mortality and morbidity burden borne by pediatric liver transplant recipients. The cumulative risk of chronic kidney disease, infection, malignancy, and cardiovascular risk factors such as hypertension, diabetes, and hyperlipidemia appear to threaten the health and well being of children more than that of acute or chronic allograft rejection. In parallel, single-center experiences have suggested that gradual immunosuppression withdrawal can be done safely with higher success rates in pediatric compared with adult liver transplant recipients. The coalescence of these two data streams has engendered substantial interest in systematic exploration of the safety and efficacy of immunosuppression withdrawal in conjunction with a vigorous scientific effort to elucidate an immunologic signature predictive of successful withdrawal. SUMMARY:There is a concerted effort within the transplant community to identify biomarkers that can accurately predict the success of immunosuppression withdrawal after liver transplantation. Freedom from lifelong immunosuppression is likely to yield considerable benefit, particularly for children who face the longest lifetime horizons.

SUBMITTER: Feng S

PROVIDER: S-EPMC2727645 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Long-term management of immunosuppression after pediatric liver transplantation: is minimization or withdrawal desirable or possible or both?

Feng Sandy S

Current opinion in organ transplantation 20081001 5

<h4>Purpose of review</h4>The aim is to review available data regarding the risks and benefits of indefinite immunosuppression against attempted immunosuppression withdrawal for children who have undergone liver transplantation.<h4>Recent findings</h4>Emerging data suggest that conventional immunosuppression practices may well be responsible for a substantial proportion of the long-term mortality and morbidity burden borne by pediatric liver transplant recipients. The cumulative risk of chronic ...[more]

PMID: 19060534

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Project description:Background and aimsAs conversion from calcineurin inhibitor to sirolimus (SRL), a mechanistic target of rapamycin inhibitor (mTOR-I), has been shown to enhance immunoregulatory profiles in liver transplant (LT) recipients (LTRs), mTOR-I therapy might allow for increased success of immunosuppression (IS) withdrawal. Our aim was to determine if operational tolerance could be observed in LTRs withdrawn from SRL and if blood/graft tolerance biomarkers were predictive of successful withdrawal.Approach and resultsWe performed a prospective trial of SRL monotherapy withdrawal in nonimmune, nonviremic LTRs > 3 years post-LT. SRL was weaned over ~6 months, and biopsies were performed 12 months postweaning or at concern for acute rejection. Twenty-one LTRs consented; 6 were excluded due to subclinical acute rejection on baseline biopsy or other reasons, and 15 underwent weaning (age 61.3 ± 8.8 years; LT to SRL weaning 6.7 ± 3 years). Eight (53%) achieved operational tolerance (TOL). Of the 7 who were nontolerant (non-TOL), 6 had mild acute rejection on biopsy near the end of weaning or at study end; 1 was removed from the trial due to liver cancer recurrence. At baseline preweaning, there were statistically increased blood tolerogenic dendritic cells and cell phenotypes correlating with chronic antigen presentation in the TOL versus non-TOL groups. A previously identified biopsy gene signature accurately predicted TOL versus non-TOL in 12/14 LTRs before weaning. At study end, biopsy staining revealed statistically significant increases in antigen-presenting cell:leukocyte pairings, FOXP3+ /CD4+ T cells, Tbet+ /CD8+ T cells, and lobular dendritic cells in the non-TOL group.ConclusionsThis study evaluated IS withdrawal directly from mTOR-I therapy in LTRs and achieved > 50% operational tolerance. Preweaning gene expression and peripheral blood mononuclear cell profiling may be useful as predictors of successful mTOR-I therapy withdrawal. NCT02062944.

Dataset Information

Long-term management of immunosuppression after pediatric liver transplantation: is minimization or withdrawal desirable or possible or both?

Publications

Long-term management of immunosuppression after pediatric liver transplantation: is minimization or withdrawal desirable or possible or both?

Similar Datasets

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