Rabbit antithymocyte globulin as induction immunotherapy in pediatric heart transplantation.
ABSTRACT There is little published data on the use of antithymocyte globulins in children. This retrospective study describes the use of Thymoglobulin (Imtix, SangStat, Lyon, France) in pediatric cardiac transplantation over a 13-year period in a single center that adjusted the dose of Thymoglobulin according to platelet count monitoring and examines the short-term hematological effects as well as longer-term outcomes.
Data for all children who received a heart transplant at the Hôpital Cardiologique at Lyon from 1984 to 2001 and who were given Thymoglobulin as part of their immunosuppressive protocol were extracted. The dose of Thymoglobulin given depended on baseline platelet count and was 2, 1.5, or 1 mg/kg per day over 5 days for the following platelet count groups: greater than 150,000/mm (normal group), 100 to 150,000/mm (mild thrombocytopenia group), and 50 to 100,000/mm (moderate thrombocytopenia group).
Thirty children of median age 14.2 years were given a median cumulative dose of Thymoglobulin of 8 mg/kg per patient; the moderate thrombocytopenia subgroup was given significantly less (6.4 mg/kg) ( P=0.032). Immediate tolerability of Thymoglobulin was good, with no cases of first-dose syndrome, anaphylaxis, or serum sickness. The platelet count decreased at the start of therapy, but recovered after discontinuation, and did not give rise to clinical concern. Patients were followed up for a median of 6.3 years (7 days-15.5 years); actuarial survival was 90%, 86%, and 74.5%, respectively, at 1, 5, and 10 years. In the first year, 50% of patients suffered an episode of rejection. The overall incidence of infection in the month following transplantation was 40%. One lymphoma occurred at 5 months.
The use of Thymoglobulin in pediatric heart-transplant patients as part of an immunosuppressive protocol, with dose adjustment according to platelet levels, has been shown to be effective in terms of rejection rate and patient survival and safe in terms of the incidence of infections and malignancy.
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ABSTRACT: Post-transplant lymphoproliferative disease (PTLD) emerged in the mid-1990s as a major graft- and life-threatening complication of pediatric kidney transplantation. This condition, usually involving uncontrolled B lymphocyte proliferation, straddles the border between infection and malignancy, since Epstein–Barr virus (EBV) is intimately associated with the pathogenesis. PTLD is seen more in younger children (more likely to be EBV seronegative), Caucasian race, and in association with the more potent immunosuppression drugs. The clinical presentation typically involves multiple enlarged lymph nodes but varies based on localization of the lymphadenopathy. The diagnosis is based primarily on histopathological features. Treatment strategies include reduction of immunosuppression, use of anti-B cell antibodies, infusion of EBV-specific cytotoxic T lymphocytes, and chemotherapy. Many different strategies have been tried to prevent PTLD, ranging from serial EBV viral load monitoring and pre-emptive immunosuppression reduction to anti-viral prophylaxis. None of the major treatment or prevention strategies has been subject to randomized clinical trials, so their relative efficacy is still unknown. PTLD remains a risk factor for graft loss, though re-transplants have not, to date, been associated with repeat PTLD.Nephrology Dialysis Transplantation 12/1998; 13(11):2968-71. · 3.37 Impact Factor
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ABSTRACT: Despite more than 40 years' experience in pediatric heart transplantation, cellular rejection remains a significant cause of morbidity and mortality. In this review, strategies and agents to prevent acute cellular rejection are discussed. Strategies to prevent rejection are divided into two phases - induction and maintenance therapies. Currently, the most commonly used induction agents are polyclonal antibodies (rabbit or equine antithymocyte globulin) and interleukin-2 receptor antibodies (daclizumab or basiliximab). Induction therapies have reduced early rejection, are renal sparing, and can reduce corticosteroid exposure, but have not yet been shown to have a longer term survival benefit. Multiple maintenance immunosuppressants are available. Nearly all regimens include a calcineurin inhibitor (either ciclosporin [cyclosporine] or tacrolimus). Most combinations in pediatric heart transplantation include an antiproliferative agent (azathioprine, mycophenolate mofetil or, less commonly, sirolimus). Everolimus has seen increasing use in adult heart transplant patients in Europe but, to date, its use is rare in pediatric heart transplantation. The use of corticosteroids as a third agent is still common, but strategies to avoid or minimize their use are increasing. The 'best' combination of therapies varies between studies. By gaining a better understanding of individuals' genetic and environmental risk factors, we may in the future be able to better predict the course of cardiac allografts and enhance our ability to tailor immunosuppression to individual patient variables with the ultimate goal of inducing a state of immune tolerance.Paediatric Drugs 12/2010; 12(6):391-403. · 1.72 Impact Factor
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ABSTRACT: OBJECTIVES: To assess the differences in rejection and infection complications between the most common contemporary immunosuppression regimen in pediatric heart transplantation (cytolytic induction, tacrolimus based) and classic triple-therapy (cyclosporine based without induction). STUDY DESIGN: We performed a retrospective, historical-control, observational study comparing outcomes in patients who underwent traditional immunosuppression (control group, n = 64) with those for whom the contemporary protocol was used (n = 39). Episodes of rejection, viremia (cytomegalovirus or Epstein-Barr virus), serious bacterial or fungal infections, anemia or neutropenia requiring treatment in the first year after heart transplantation, and 1-year survival were compared between traditional and contemporary immunosuppression groups. RESULTS: The 2 groups were similar with respect to baseline demographics. There were no differences in risk of cytomegalovirus, Epstein-Barr virus, or bacterial or fungal infections in the first year post-transplantation. Patients in the contemporary group were more likely to need therapy for anemia (51% vs 14%, P < .001) or neutropenia (10% vs 0%, P = .019). However, more contemporary protocol patients were rejection-free in the first year post-transplantation (63% vs 41%, P = .03). Overall graft survival was similar between groups (P = .15). CONCLUSIONS: A contemporary immunosuppression regimen using tacrolimus, mycophenolate mofetil, and induction was associated with less rejection in the first year, with no difference in the risk of infection but greater risk of anemia and neutropenia requiring treatment. Long-term follow-up on these patients will evaluate the impact of the immunosuppression regimen on survival.The Journal of pediatrics 02/2013; · 4.02 Impact Factor