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Robert J Gajarski,
Elizabeth D Blume,
Simon Urschel,
Kenneth Schechtman,
Jie Zheng, Lori J West,
Louis Altamirano,
Shelley Miyamoto,
David C Naftel,
James K Kirklin,
Mary C Zamberlan,
Charles E Canter
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ABSTRACT: Variable rates of malignancy and early infection have previously been reported in heart transplant (HTx) recipients who received induction therapy. This study hypothesized that induced pediatric patients would have an increased risk of these events compared with non-induced patients.
Data from a prospective, multicenter event-driven registry of outcomes after HTx listing in patients aged < 18 years was used to analyze risks of infection and malignancy and their association with induction between January 1993 and December 2007.
Of 2,374 patients, 1,258 (53%) received induction and more frequently from 1999 to 2008 compared with 1993 to 1998 (70.8% vs 57.5%, p < 0.001). At HTx, induced patients were more likely to have congenital heart disease (56.9% vs 48.1%, p < 0.001) but no more likely to be positive for Epstein-Barr virus (50.3% vs 51.4%, p = 0.67). Post-transplant lymphoproliferative disease (PTLD) was the most common malignancy (n = 92) within 5 years of HTx. Patients who received induction had a lower risk for PTLD (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.84; p = 0.009) and early fungal infections (HR, 0.60; 91% CI, 0.40-0.91; p = 0.016). Among induction agents used, OKT3 was associated with lowest freedom from PTLD and fungal/cytomegalovirus infection.
Induction use has increased since 1999 and has not been associated with an increased risk of malignancy (predominantly PTLD) or overall infection. Because these adverse events occurred with higher rates in non-induced patients, it is likely that induction alone is not the primary risk determinant for PTLD and infection.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 03/2011; 30(3):299-308. · 3.54 Impact Factor
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ABSTRACT: Safety and immunogenicity of diphtheria and tetanus booster vaccination were evaluated in 28 children after thoracic transplantation. Adverse events were documented in a patient diary. Blood was collected prior to and four wk after vaccination. Specific antibody concentrations were measured by ELISA. Lymphocytes were investigated for expression of activation markers (CD25, HLA-DR) by flow cytometry and proliferation assays with and without stimulation. Post-vaccination antibody titers were higher than prevaccination (p < 0.001), with more patients having protective antibody levels against diphtheria (p < 0.02) and tetanus (p < 0.001). There was no increased proliferation in non-stimulated or stimulated cultures after vaccination. The number of T-lymphocytes activated by the vaccination antigens was similar pre- and post-vaccination, whereas HLA-DR-expression on stimulated and non-stimulated CD4(+) T-cells increased significantly. Increase in antibodies was negatively correlated with tacrolimus dose, and impaired cellular immunity was associated with higher tacrolimus dose and steroid use. Adverse events were similar to the general population; serious adverse events and rejection did not occur. Vaccination with inactivated vaccines can be performed safely in immunosuppressed children after thoracic transplantation and induces protective antibody levels in the majority of patients. Impaired induction of specific cellular immunity is correlated with intensity of immunosuppression and may explain reduced sustainability of antibodies.
Pediatric Transplantation 01/2011; 15(3):272-80. · 1.48 Impact Factor
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ABSTRACT: Effective immunosuppression is the key to successful organ transplantation, with success being defined as minimal rejection risk with concomitant minimal drug toxicities. Despite the general recognition of this fact, a paucity of appropriate clinical trials in children has contributed to lack of standardization of clinical management regimens, resulting in an extensive diversity of favored approaches. Nonetheless, although consensus has not been reached on the ideal approach to immunosuppression in pediatric transplantation, new drug therapies have contributed to a continuing improvement in graft and patient survival. Future clinical research must focus on diminishing the extensive burden of toxicities of these therapeutic agents in children.
Pediatric Clinics of North America 04/2010; 57(2):433-57, table of contents. · 2.24 Impact Factor
