Withdrawal of immunosuppression in liver transplantation: Lessons learned from PTLD

Mazariegos, George

doi:10.1111/j.1399-3046.2004.00173.x

Cited by 9 publications

(3 citation statements)

References 38 publications

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“…Such knowledge did not dissuade parents during the decision phase, nor did it weaken their resolve when complications occurred during or after transplantation. Furthermore, long‐term survival and quality of life post‐transplant should continue to improve due to improved monitoring for EBV‐ and CMV‐related complications (37), elimination of corticosteroids from immunosuppressive regimens and efforts to minimize immunosuppressive medication for individual patients (18,37).…”

Section: Discussionmentioning

confidence: 99%

Elective Liver Transplantation for the Treatment of Classical Maple Syrup Urine Disease

Strauss

Mazariegos²,

Sindhi³

et al. 2006

American Journal of Transplantation

110

123

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An 8.5-year-old girl with classical maple syrup urine disease (MSUD) required liver transplantation for hypervitaminosis A and was effectively cured of MSUD over an 8-year clinical follow-up period. We developed a collaborative multidisciplinary effort to evaluate the effects of elective liver transplantation in 10 additional children (age range 1.9-20.5 years) with classical MSUD. Patients were transplanted with whole cadaveric livers under a protocol designed to optimize safe pre-and post-transplant management of MSUD. All patients are alive and well with normal allograft function after 106 months of follow-up in the index patient and a median follow-up period of 14 months (range 4-18 months) in the 10 remaining patients. Leucine, isoleucine and valine levels stabilized within 6 hours post-transplant and remained so on an unrestricted protein intake in all patients. Metabolic cure was documented as a sustained increase in weight-adjusted leucine tolerance, normalization of plasma concentration relationships among branched-chain and other essential and nonessential amino acids, and metabolic and clinical stability during protein loading and intercurrent illnesses. Costs and risks associated with surgery and immune suppression were similar to other pediatric liver transplant populations.

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Section: Discussionmentioning

confidence: 99%

Elective Liver Transplantation for the Treatment of Classical Maple Syrup Urine Disease

Strauss

Mazariegos²,

Sindhi³

et al. 2006

American Journal of Transplantation

110

123

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“…Mazariegos, in a report on attempted immunosuppression withdrawal, found that: patients with negative DSA could be easily weaned off immunosuppression; most patients who failed weaning off immunosuppression were DSA positive [5]. De novo DSA was identified as an independent risk factor for late graft dysfunction and decreased patient and graft survival at 1 year [6].…”

Section: Graft Healthmentioning

confidence: 99%

Long Term Outcomes after Pediatric Liver Transplantation

Yazigi

2013

Pediatr Gastroenterol Hepatol Nutr

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Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle.

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“…Analysis of peripheral blood DC in organ or BM transplant patients may be a helpful immune monitoring tool [103, 104]; reviewed in ref [6]. Higher incidences of circulating pDC relative to mDC are found in operationally tolerant pediatric liver allograft recipients and in patients on low dose immunosuppressive drug therapy undergoing prospective drug weaning, compared with patients on maintenance immunosuppression.…”

Section: Evidence Of Immune Regulation By DC In Humans and In Climentioning

confidence: 99%

Tolerogenic dendritic cells and their role in transplantation

Ezzelarab

Thomson

2011

Seminars in Immunology

146

130

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The pursuit of clinical transplant tolerance has led to enhanced understanding of mechanisms underlying immune regulation, including the characterization of immune regulatory cells, in particular antigen-presenting cells (APC) and regulatory T cells (Treg), that may play key roles in promoting operational tolerance. Dendritic cells (DC) are highly-efficient APC that have been studied extensively in rodents and humans, and more recently in non-human primates. Owing to their ability to regulate both innate and adaptive immune responses, DC are considered to play crucial roles in directing the alloimmune response towards transplant tolerance or rejection. Mechanisms via which they can promote central and peripheral tolerance include clonal deletion, the induction of Treg, and inhibition of memory T cell responses. These properties have led to the use of tolerogenic DC as a therapeutic strategy to promote organ transplant tolerance. In rodents, infusion of donor- or recipient-derived tolerogenic DC can extensively prolong donor-specific allograft survival, in association with regulation of the host T cell response. In clinical transplantation, progress has been made in monitoring DC in relation to graft outcome, including studies in operational liver transplant toleranceAlthough clinical trials involving immunotherapeutic DC for patients with cancer are ongoing, implementation of human DC therapy in clinical transplantation will require assessment of various critical issues. These include cell isolation and purification techniques, source, route and timing of administration, and combination immunosuppressive therapy. With ongoing non-human primate studies focused on DC therapy, these logistics can be investigated seeking the optimal approaches. The scientific rationale for implementation of tolerogenic DC therapy to promote clinical transplant tolerance is strong. Evaluation of technical and therapeutic logistic issues is an important next step prior to the application of “therapeutic” DC in clinical organ transplantation.

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Withdrawal of immunosuppression in liver transplantation: Lessons learned from PTLD

Cited by 9 publications

References 38 publications

Elective Liver Transplantation for the Treatment of Classical Maple Syrup Urine Disease

Elective Liver Transplantation for the Treatment of Classical Maple Syrup Urine Disease

Long Term Outcomes after Pediatric Liver Transplantation

Tolerogenic dendritic cells and their role in transplantation

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