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OKT3 and viral disease in pediatric liver transplant recipients
James S Bowman1, Michael Green, Velma P Scantlebury
1Departments of Surgery and Pediatrics, University of Pittsburgh School of Medicine, Division of Infectious Diseases, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract:
Seventy-four consecutive pediatric liver transplant recipients were reviewed to assess the effect of the monoclonal anti-T-lymphocyte antibody OKT3 on subsequent viral infection (9 patients were excluded due to postoperative demise during the 1st week). Twenty-two patients received OKT3 in addition to standard cyclosporine-prednisone immunosuppression for either steroid-resistant acute rejection (18) or to facilitate reduction of cyclosporine due to severe renal impairment (4). Invasive infections were diagnosed by histology or culture in tissue biopsies or bronchoalveolar lavage specimens. The overall incidence of viral infection was 58%, half of which was due to cytomegalovirus (CMV). Invasive viral disease was associated with increased mortality (37% vs. 3% p = 0.001). Viral-related deaths were due to CMV (5), disseminated adenovirus (3), disseminated enterovirus (1) and respiratory syncytial viral pneumonia (1). The use of OKT3 was associated with increased viral disease (59% vs. 33% p=0.04) and invasive primary CMV disease (58% vs. 19% p=0.04). Trends were observed toward increased overall viral infection (73% vs. 51 % p=0.08), primary CMV infection (58% vs. 25% p=0.08) and overall mortality (27% vs. 9% p =0.08) following OKT3 therapy. We conclude that pediatric liver transplant recipients who require OKT3 therapy may be at increased risk for invasive viral disease and especially invasive primary CMV disease.
Insights
The monoclonal antibody OKT3 increases the risk of viral infections, particularly cytomegalovirus (CMV), in pediatric liver transplant recipients. This heightened risk of invasive viral disease may also be linked to increased mortality.
Area of Science:
- Immunology
- Transplant Surgery
- Pediatric Medicine
- Infectious Diseases
Background:
- Pediatric liver transplantation requires potent immunosuppression to prevent rejection.
- The monoclonal antibody OKT3 is used to manage acute rejection or renal impairment.
- Viral infections are a significant cause of morbidity and mortality post-transplant.
Purpose of the Study:
- To evaluate the impact of OKT3 therapy on the incidence of viral infections in pediatric liver transplant recipients.
- To assess the association between OKT3 use and specific viral pathogens, including cytomegalovirus (CMV).
- To determine if OKT3 therapy correlates with increased mortality in this patient population.
Main Methods:
- Retrospective review of 74 pediatric liver transplant recipients (excluding 9 early deaths).
- Analysis of patients receiving OKT3 for steroid-resistant rejection or cyclosporine reduction.
- Diagnosis of invasive infections via histology or culture from tissue biopsies or bronchoalveolar lavage.
Main Results:
- Overall viral infection incidence was 58%, with CMV accounting for half.
- Invasive viral disease was linked to significantly higher mortality (37% vs. 3%, p=0.001).
- OKT3 use was associated with increased viral disease (59% vs. 33%, p=0.04) and primary CMV disease (58% vs. 19%, p=0.04).
Conclusions:
- Pediatric liver transplant recipients treated with OKT3 face an elevated risk of invasive viral infections.
- There is a particular concern for invasive primary cytomegalovirus (CMV) disease in patients receiving OKT3.
- OKT3 therapy may be associated with increased overall mortality in this vulnerable group.
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