Post-transplant lymphoproliferative disorder in pediatric heart transplant recipients
Post-transplantation lymphoproliferative disorder (PTLD) is a major cause of morbidity and mortality after pediatric heart transplantation.
Heart transplant recipients at The Hospital for Sick Children, Toronto, from 1990 to May 2008, were reviewed. Competing risk hazard analysis was used to model the natural history of the disease. Patients were matched for gender and duration of follow-up to identify potential covariates associated with increased risk of PTLD.
A total of 173 heart transplant recipients (42% <1 year old) were reviewed. Twenty-three developed PTLD at a median of 4 years post-transplantation. After transplantation, PTLD affected 9%, 15% and 28% at 3, 5 and 10 years, respectively. Freedom from death or PTLD recurrence was 72%, 58% and 50% at 1, 3 and 5 years, respectively, after PTLD diagnosis. Higher maximum Epstein-Barr viral (EBV) load (hazard ratio [HR]: 2.6, p = 0.004) and longer duration of induction therapy (HR: 1.7, p = 0.02) were associated with increased risks of PTLD. Higher cumulative cyclosporine doses over the first year post-transplantation were associated with increased risks of PTLD (HR: 1.2 per 1 mg/kg/day equivalent, p = 0.03), but higher tacrolimus doses were not (p = 0.38). Patients on cyclosporine at 6 months post-transplantation were at higher risk of PTLD than those on tacrolimus (HR: 5.2, p = 0.003). The use of anti-viral prophylaxis in patients with high EBV load may provide some protection (HR: 7.6 vs 15.4 with no anti-viral, p = 0.02).
PTLD is a major concern in pediatric heart transplant recipients and is associated with high morbidity/mortality. Exposure to EBV and higher intensity of immunosuppression seems to be associated with increased risk.
Available from: Britta Maecker-Kolhoff
- "In children, the effectiveness of RIS is even less clear. Anecdotal data report survival rates of 30–73% with RIS alone [36, 47–49]. "
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ABSTRACT: Patients after solid organ transplantation (SOT) carry a substantially increased risk to develop malignant lymphomas. This is in part due to the immunosuppression required to maintain the function of the organ graft. Depending on the transplanted organ, up to 15% of pediatric transplant recipients acquire posttransplant lymphoproliferative disease (PTLD), and eventually 20% of those succumb to the disease. Early diagnosis of PTLD is often hampered by the unspecific symptoms and the difficult differential diagnosis, which includes atypical infections as well as graft rejection. Treatment of PTLD is limited by the high vulnerability towards antineoplastic chemotherapy in transplanted children. However, new treatment strategies and especially the introduction of the monoclonal anti-CD20 antibody rituximab have dramatically improved outcomes of PTLD. This review discusses risk factors for the development of PTLD in children, summarizes current approaches to therapy, and gives an outlook on developing new treatment modalities like targeted therapy with virus-specific T cells. Finally, monitoring strategies are evaluated.
Clinical and Developmental Immunology 09/2013; 2013(10):814973. DOI:10.1155/2013/814973 · 2.93 Impact Factor
Available from: PubMed Central
- "Taking a precise look at the survival curves illustrated in the figure 1, no mortality has been occurred in heart transplant children who had received rituximab during the first 4-5 years after PTLD diagnosis. This finding is of utmost importance when we consider the fact that PTLD is highly fatal in heart graft recipients compared to recipients of other organs (49). This makes rituximab an indispensible drug to manage PTLD arising in heart transplant recipients. "
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ABSTRACT: Rituximab, an anti-CD20 agent, has been suggested as an effective strategy to deal with post transplant lymphoproliferative disorders (PTLD). In the current study, we aim to evaluate the efficacy of rituximab therapy in heart transplant population developing PTLD. A comprehensive search of the literature was performed to gather the available data on lymphoproliferative disorders occurring in heart transplant patients. Finally, data of 125 patients from 26 previously published studies were included into the study. Patients who underwent rituximab therapy had significantly worse tumoral histopathology features (P-value= 0.003).
Survival analyses showed no significant difference regarding receiving rituximab therapy for heart recipients; however, when the analysis was repeated only including data of pediatric patients, significant beneficial effects for pediatric were found for rituximab therapy. In fact, no children undergoing rituximab therapy died during the follow up. In conclusion, this study showed that rituximab therapy in pediatric heart transplant recipients with PTLD represents surprisingly excellent results, making rituximab an indispensable agent in the management of the disease. To define feasibility of rituximab therapy in adult recipients of heart graft with PTLD, randomized controlled trials are needed.
Reliability Symposium, 1996. Reliability - Investing in the Future., IEEE 34th Annual Spring; 05/1996
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