EF<40%, permanent atrial fibrillation, and QRS>or=150 ms are independent predictors for VT/VF occurrence in predominantly secondary prophylactic ICD patients. Combining all independent predictors, we developed a risk score for VT/VF occurrence identifying a subgroup of patients with two or more risk factors who had a 100% 2-year risk. Future studies will reveal if this risk score helps to identify ICD patients suitable for empirical anti-arrhythmic therapy and to improve patient selection for prophylactic ICD therapy.
No abstract
Posttransplant lymphoproliferative disorders (PTLD) have been recognized as severe side effects of immunosuppressive therapy after organ transplantation. However, no standard diagnostic and therapeutic approaches have been defined. Furthermore, few interdisciplinary perspectives comparing patients with heart/liver/kidney transplants are available. Here, we present results of a multicenter, retrospective analysis of pediatric patients treated for PTLD in Germany and Switzerland from 1990 to 2003. Patients were recruited by surveys through the working groups of pediatric renal, liver, and heart/lung transplantation as well as from the registry of pediatric Non-Hodgkin’s lymphomas (NHL-BFM). Inclusion criteria consisted of a history of solid organ transplantation, biopsy-proven diagnosis of PTLD, and age at onset of PTLD 18 years of less. Patient charts were analyzed for clinical course from transplant to onset of PTLD, virus serology, treatment regimen, and outcome. A total of 53 patients from 19 centers could be included, among them 25 renal graft recipients, 14 heart-, 11 liver-, and 1 lung transplant recipients as well as 2 patients after combined heart/lung transplantation. PTLD was diagnosed at a median time of 34 months [range 2 – 119 months] post organ transplantation. Histological evaluation based on the WHO classification showed 2 early lesion PTLD, 8 polymorphic PTLD, 26 high-grade B-cell lymphomas, 12 Burkitt-like lymphomas, 3 cases of Hodgkin’s disease and 2 T-cell lymphomas. Cytogenetic analysis revealed translocations involving chromosome 8 in five patients with Burkitt-like lymphomas. EBV gene products were detected in 31 tumors by in situ hybridization or immunohistochemistry, while 13 tumors were EBV negative (no data available on 9 tumors). EBV serology was negative in 55% of patients at the time of organ transplantation. However, in 29 patients EBV primary infection/reactivation was documented after organ transplantation (median time to infection/reactivation 5.9 months). In all patients immunosuppressive therapy was reduced. Treatment and follow up data were available in 51 patients: six patients remained in complete remission without additional treatment, in one patient autologous EBV-specific T-cells were infused. 41 patients received monoclonal antibodies (anti-CD20; n=7), chemotherapy (n=28), or a combination thereof (n=5). Fifteen of 51 patients died of progressing PTLD (n=7; among them 3 patients in which treatment was refused), treatment-related mortality (n=7), or fatal graft failure (n=2). Mortality was higher in patients with Burkitt-like lymphomas (7 of 12 patients) compared to all other entities (8 of 39 patients; p=0.026). Patients with stage IV disease had an inferior outcome compared to patients with stage I-III disease (mortality 6 of 7 vs. 9 of 44 patients, p=0.002). Thus, pediatric PTLD is a heterogeneous disease often associated with fatal outcome. The PED-PTLD study group has initiated a prospective multicenter trial of standardized diagnosis and treatment of PTLD after solid organ transplantation in children.
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