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Abstracts
A murine model for the prevention of transfusion-transmitted CMV infection
Presented at: 31st Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT), 3/20/05 - 3/23/05
Background: Transfusion-transmitted CMV infection continues to cause significant morbidity and mortality in immunocompromised transfusion recipients. In order to better understand the mechanisms of TT-CMV, and to validate the efficacy of methods to prevent TT-CMV, we have utilized a mouse transfusion model. We have evaluated the efficacy of photochemical treatment with amotosalen HCl and UVA light to prevent transfusion-transmitted cytomegalovirus (TT-CMV) infection.
Materials and Methods: Balb/c donor mice were infected by intra-peritoneal injection with murine CMV (MCMV; 106 pfu), and rested for 14 days to allow for development of viral latency. Peripheral blood was harvested from donors and transfused by intravenous infusion into either syngeneic (Balb/c) or allogeneic (C57BL/6) recipients. The kinetics of MCMV DNA detection in the spleen, salivary glands, plasma, and white blood cells of recipients was analyzed on days 1, 3, 5 and 7 (n=5 mice per time point on days 1, 3, 5; and n=10 on day 7) post-transfusion. To assess prevention of TT-CMV donor leukocyte fractions were prepared with amotosalen HCl (150 µM) and a 3 J/cm2 UVA treatment.
Results: WBCs isolated from donor blood were positive for MCMV DNA, while plasma was negative. In syngeneic transfusion recipients, MCMV DNA was detectable on day 1 in spleens (4/5), salivary glands (2/5), and white blood cells (2/5). By day 7, the majority of spleens (8/10) and white blood cells (8/10) were positive for MCMV DNA and all salivary glands (10/10) were positive. In allogeneic recipients, MCMV DNA detection was more variable and at lower levels (day 7: WBC (6/10), spleen (7/10), salivary gland (5/10)). If donor leukocytes were treated with amotosalen HCl and UVA light prior to transfusion, MCMV DNA was uniformly absent in all recipient tissues after transfusion.
Conclusions: The frequency of MCMV DNA detection varies in syngeneic versus allogeneic transfusion recipients. However, following amotosalen/UVA treatment of the donor leukocytes, MCMV DNA is not detected in recipients. These data provide further support for the use of amotosalen/UVA to prevent TT-CMV in immunocompromised patients, including bone marrow and hematopoietic transplant recipients. This technology appears to be more effective than filtration or process leuko-reduction for prevention of TT-CMV.
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