TRANSFUSION PRACTICE Direct assessment of cytomegalovirus transfusion-transmitted risks after universal leukoreduction Yanyun Wu, Shimian Zou, Ritchard Cable, Kerri Dorsey, Yanlin Tang, Cheryl Anne Hapip, Russell Melmed, Jonathan Trouern-Trend, Jian-Hui Wang, Melanie Champion, Chyang Fang, and Roger Dodd BACKGROUND: Cytomegalovirus (CMV) transfusion- transmitted disease (TTD) remains a clinical concern. Universal leukoreduction has become one of the main strategies for the prevention of CMV-TTD. Through pro- spective clinical follow-up and testing of transfusion recipients (TRs), the risk for CMV-TTD was studied. STUDY DESIGN AND METHODS: Transfused units were all leukoreduced and not prospectively screened for CMV. For TRs with negative baseline CMV testing results (CMV total antibody and DNA), all follow-up TR samples were tested for CMV total antibody and DNA, and retained linked donor serum samples were tested for CMV total antibody. In cases when CMV-TTD was suspected, donor sera were also tested for CMV DNA and selected TR samples were tested for CMV immu- noglobulin M antibody. Evaluable transfusion was defined as a transfusion with TR sample(s) collected 14 to 180 days posttransfusion. RESULTS: Forty-six TRs were negative for CMV at baseline. There were 1316 evaluable cellular blood transfusions to these TRs. Of 1316 evaluable cellular products, 460 (35%) were positive for CMV total anti- body tested using linked donor samples. Three cases of probable CMV-TTD were found; however, there was no definitive proof from donor follow-up that they were transfusion associated. CONCLUSION: Among all 46 baseline seronegative recipients and 1316 evaluable transfusions, the calcu- lated overall CMV-TTD risk was up to 6.5% (95% confi- dence interval [CI], 1.0%-18.0%) in terms of TRs and up to 0.23% (95% CI, 0.06%-0.62%) in terms of non– CMV-screened leukoreduced cellular products. In summary, after universal leukoreduction, CMV-TTD, while uncommon, may still occur. C ytomegalovirus (CMV) can be transmitted through blood transfusion. 1-10 Just like trans- missions through other routes, most CMV transfusion-transmitted diseases (CMV-TTD) are self-limited. 7,9,11-13 However, primary CMV transmis- sion through blood transfusion can cause significant morbidity and mortality in immunocompromised patients such as transplant recipients, AIDS patients, and low-birth-weight neonates. 4,7,9,12-16 The clinical manifesta- tion of CMV-TTD can range from asymptomatic, to a mononucleosis-like nonspecific syndrome, to dissemi- nated diseases involving multiple organs. It can present with fever, malaise, lymphadenopathy, rash, pharyngitis, retinitis, polyneuropathy, hepatitis, interstitial pneu- monitis, menigoencephalitis, colitis, gastritis, nephritis, lymphocytosis, leukopenia, thrombocytopenia, and hemolytic anemia. 7,12,13,17 CMV-TTD can occur 3 to 8 weeks after transfusion with CMV immunoglobulin G (IgG) antibody detected within 3 to 4 months of transfusion. 1,2,12,13,18-20 The reported rate of CMV-TTD was as high as 10% to 60% historically. 7,21-25 ABBREVIATIONS: TR(s) = transfusion recipient(s); TTD = transfusion-transmitted disease. From theYale University School of Medicine, New Haven, Connecticut; Jerome H. Holland Laboratory, American Red Cross Blood Services, Rockville, Maryland; and The Connecticut Region, American Red Cross Blood Services, Farmington, Connecticut. Address reprint requests to: YanYun Wu, MD, PhD, Associate Professor of Laboratory Medicine, Department of Laboratory Medicine, Yale University School of Medicine, 20 York Street, CB 459, New Haven, CT 06510-3202; e-mail: yan.wu@yale.edu. The study was supported by the American Red Cross Blood Services. Received for publication May 14, 2009; revision received September 2, 2009, and accepted September 9, 2009. doi: 10.1111/j.1537-2995.2009.02486.x TRANSFUSION 2010;50:776-786. 776 TRANSFUSION Volume 50, April 2010