AABB Committee Report: reducing transfusion-transmitted cytomegalovirus infections
AABB, Clinical Transfusion Medicine Committee
Search for more papers by this authorNancy M. Heddle
Department of Medicine, McMaster Centre for Transfusion Research
Canadian Blood Services & Division of Clinical Pathology, McMaster University, Hamilton, Ontario, Canada
Search for more papers by this authorMichael Boeckh
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and the University of Washington, Seattle, Washington
Search for more papers by this authorBrenda Grossman
Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University in St Louis, St Louis, Missouri
Search for more papers by this authorJessica Jacobson
Department of Pathology, Bellevue Hospital Center, New York University School of Medicine, New York, New York
Search for more papers by this authorSteven Kleinman
University of British Columbia, Victoria, Canada, and Medical Advisor to AABB, Bethesda, Maryland
Search for more papers by this authorAaron A.R. Tobian
Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University, Baltimore, Maryland
Search for more papers by this authorKathryn Webert
Canadian Blood Services & Division of Clinical Pathology, McMaster University, Hamilton, Ontario, Canada
Search for more papers by this authorEdward C.C. Wong
Division of Laboratory Medicine, Departments of Pediatrics and Pathology, Children's National Medical Center, George Washington School of Medicine and Health Sciences, Washington, DC
Search for more papers by this authorCorresponding Author
John D. Roback
Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, Atlanta, Georgia
Address reprint requests to: John D. Roback, MD, PhD, Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, EUH D-655, 1364 Clifton Rd NE, Atlanta, GA 30322; e-mail: [email protected]Search for more papers by this authorAABB, Clinical Transfusion Medicine Committee
Search for more papers by this authorNancy M. Heddle
Department of Medicine, McMaster Centre for Transfusion Research
Canadian Blood Services & Division of Clinical Pathology, McMaster University, Hamilton, Ontario, Canada
Search for more papers by this authorMichael Boeckh
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and the University of Washington, Seattle, Washington
Search for more papers by this authorBrenda Grossman
Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University in St Louis, St Louis, Missouri
Search for more papers by this authorJessica Jacobson
Department of Pathology, Bellevue Hospital Center, New York University School of Medicine, New York, New York
Search for more papers by this authorSteven Kleinman
University of British Columbia, Victoria, Canada, and Medical Advisor to AABB, Bethesda, Maryland
Search for more papers by this authorAaron A.R. Tobian
Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University, Baltimore, Maryland
Search for more papers by this authorKathryn Webert
Canadian Blood Services & Division of Clinical Pathology, McMaster University, Hamilton, Ontario, Canada
Search for more papers by this authorEdward C.C. Wong
Division of Laboratory Medicine, Departments of Pediatrics and Pathology, Children's National Medical Center, George Washington School of Medicine and Health Sciences, Washington, DC
Search for more papers by this authorCorresponding Author
John D. Roback
Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, Atlanta, Georgia
Address reprint requests to: John D. Roback, MD, PhD, Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, EUH D-655, 1364 Clifton Rd NE, Atlanta, GA 30322; e-mail: [email protected]Search for more papers by this authorFor the AABB CMV Prevention Work Group.
Abstract
Transfusion-transmitted cytomegalovirus (TT-CMV) is often asymptomatic, but certain patient populations, such as very low birth weight neonates, fetuses requiring intrauterine transfusion, pregnant women, patients with primary immunodeficiencies, transplant recipients, and patients receiving chemotherapy or transplantation for malignant disease, may be at risk of life-threatening CMV infection. It is unclear whether leukoreduction of cellular blood components is sufficient to reduce TT-CMV or whether CMV serological testing adds additional benefit to leukoreduction. The AABB CMV Prevention Work Group commissioned a systematic review to address these issues and subsequently develop clinical practice guidelines. However, the data were of poor quality, and no studies of significant size have been performed for over a decade. Rather than creating guidelines of questionable utility, the Work Group (with approval of the AABB Board of Directors) voted to prepare this Committee Report. There is wide variation in practices of using leukoreduced components alone or combining CMV-serology and leukoreduction to prevent TT-CMV for at-risk patients. Other approaches may also be feasible to prevent TT-CMV, including plasma nucleic acid testing, pathogen inactivation, and patient blood management programs to reduce the frequency of inappropriate transfusions. It is unlikely that future large-scale clinical trials will be performed to determine whether leukoreduction, CMV-serology, or a combination of both is superior. Consequently, alternative strategies including pragmatic randomized controlled trials, registries, and collaborations for electronic data merging, nontraditional approaches to inform evidence, or development of a systematic approach to inform expert opinion may help to address the issue of CMV-safe blood components.
REFERENCES
- 1Ho M. Epidemiology of cytomegalovirus infections. Rev Infect Dis 1990; 12 Suppl 7: S701–10.
- 2Roback JD, Josephson CD. New insights for preventing transfusion-transmitted cytomegalovirus and other white blood cell-associated viral infections. Transfusion 2013; 53: 2112–6.
- 3Slobedman B, Mocarski ES. Quantitative analysis of latent human cytomegalovirus. J Virol 1999; 73: 4806–12.
- 4Wu, Y, Zou, Cable, S, Dorsey, R, et al. Direct assessment of cytomegalovirus transfusion-transmitted risks after universal leukoreduction. Transfusion 2010; 50: 776–86.
- 5Dumont LJ, Luka J, VandenBroeke T, et al. The effect of leukocyte-reduction method on the amount of human cytomegalovirus in blood products: a comparison of apheresis and filtration methods. Blood 2001; 97: 3640–7.
- 6 National Academies of Sciences, Engineering, and Medicine; Institute of Medicine. Clinical practice guidelines we can trust. 2011. Washington, DC: National Academies Press.
- 7Wiegmann TL, Mintz PD. The growing role of AABB clinical practice guidelines in improving patient care. Transfusion 2015; 55: 935–6.
- 8Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336: 924–6.
- 9Terracciano L, Brozek J, Compalati E, et al. GRADE system: new paradigm. Curr Opin Allergy Clin Immunol 2010; 10: 377–83.
- 10Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol 2011; 64: 395–400.
- 11Roback JD, Caldwell S, Carson J, et al. Evidence-based practice guidelines for plasma transfusion. Transfusion 2010; 50: 1227–39.
- 12Carson JL, Grossman BJ, Kleinman S, et al. Red blood cell transfusion: a clinical practice guideline from the AABB*. Ann Intern Med 2012; 157: 49–58.
- 13Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Intern Med 2015; 162: 205–13.
- 14Mainou M, Alahdab F, Tobian A, et al. Reducing the risk of transfusion transmitted cytomegalovirus (CMV) infection: a systematic review and meta-analysis. Transfusion. In press 2016.
- 15Xu D, Yonetani M, Uetani Y, et al. Acquired cytomegalovirus infection and blood transfusion in preterm infants. Acta Paediatr Jpn 1995; 37: 444–9.
- 16Eisenfeld L, Silver H, McLaughlin J, et al. Prevention of transfusion-associated cytomegalovirus infection in neonatal patients by the removal of white cells from blood. Transfusion 1992; 32: 205–9.
- 17Bowden RA, Slichter SJ, Sayers MH, et al. Use of leukocyte-depleted platelets and cytomegalovirus-seronegative red blood cells for prevention of primary cytomegalovirus infection after marrow transplant. Blood 1991; 78: 246–50.
- 18Gilbert GL, Hayes K, Hudson IL, et al. Prevention of transfusion-acquired cytomegalovirus infection in infants by blood filtration to remove leucocytes. Neonatal cytomegalovirus infection study group [see comments]. Lancet 1989; 1: 1228–31.
- 19Murphy MF, Grint PC, Hardiman AE, et al. Use of leucocyte-poor blood components to prevent primary cytomegalovirus (CMV) infection in patients with acute leukaemia [letter]. Br J Haematol 1988; 70: 253–4.
- 20Ohto H, Ujie N, Hirai K. Lack of difference in cytomegalovirus transmission via the transfusion of filtered-irradiated and nonfiltered-irradiated blood to newborn infants in an endemic area. Transfusion 1999; 39: 201–5.
- 21Nichols WG, Price TH, Gooley T, et al. Transfusion-transmitted cytomegalovirus infection after receipt of leukoreduced blood products. Blood 2003; 101: 4195–200.
- 22Bowden RA, Slichter SJ, Sayers M, et al. A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion- associated CMV infection after marrow transplant. Blood 1995; 86: 3598–603.
- 23Kekre N, Tokessy M, Mallick R, et al. Is cytomegalovirus testing of blood products still needed for hematopoietic stem cell transplant recipients in the era of universal leukoreduction? Biol Blood Marrow Transplant 2013; 19: 1719–24.
- 24Ljungman P, Larsson K, Kumlien G, et al. Leukocyte depleted, unscreened blood products give a low risk for CMV infection and disease in CMV seronegative allogeneic stem cell transplant recipients with seronegative stem cell donors. Scand J Infect Dis 2002; 34: 347–50.
- 25Pamphilon D, Foot A, Adeodu A, et al. Prophylaxis and prevention of CMV infection in BM allograft recipients: leukodepleted platelets are equivalent to those form CMV-seronegative donors. Bone Marrow Transplant 1999; S66: 213.
- 26Yeager AS, Palumbo PE, Malachowski N, et al. Sequelae of maternally derived cytomegalovirus infections in premature infants. J Pediatr 1983; 102: 918–22.
- 27Simanek AM, Dowd JB, Pawelec G, et al. Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States. PLoS One 2011; 6: e16103.
- 28Arens R, Remmerswaal EB, Bosch JA, et al. 5th international workshop on CMV and Immunosenescence—a shadow of cytomegalovirus infection on immunological memory. Eur J Immunol 2015; 45: 954–7.
- 29Barnes LL, Capuano AW, Aiello AE, et al. Cytomegalovirus infection and risk of alzheimer disease in older black and white individuals. J Infect Dis 2015; 211: 230–7.
- 30Smith D, Lu Q, Yuan S, et al. Survey of current practice for prevention of transfusion-transmitted cytomegalovirus in the united states: leucoreduction vs. cytomegalovirus-seronegative. Vox Sang 2010; 98: 29–36.
- 31Lieberman L, Devine DV, Reesink HW, et al. Prevention of transfusion-transmitted cytomegalovirus (CMV) infection: standards of care. Vox Sang 2014; 107: 276–311.
- 32Josephson CD, Caliendo AM, Easley KA, et al. Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. JAMA Pediatr 2014; 168: 1054–62.
- 33Nash T, Hoffmann S, Butch S, et al. Safety of leukoreduced, cytomegalovirus (CMV)-untested components in CMV-negative allogeneic human progenitor cell transplant recipients. Transfusion 2012; 52: 2270–2.
- 34Thiele T, Kruger W, Zimmermann K, et al. Transmission of cytomegalovirus (CMV) infection by leukoreduced blood products not tested for CMV antibodies: a single-center prospective study in high-risk patients undergoing allogeneic hematopoietic stem cell transplantation (CME). Transfusion 2011; 51: 2620–6.
- 35Hall S, Danby R, Osman H, et al. Transfusion in CMV seronegative T-depleted allogeneic stem cell transplant recipients with CMV-unselected blood components results in zero CMV transmissions in the era of universal leukocyte reduction: a UK dual centre experience. Transfus Med 2015 Jun 26. doi: 10.1111/tme.12219. [Epub ahead of print].
- 36Ziemann M, Heuft HG, Frank K, et al. Window period donations during primary cytomegalovirus infection and risk of transfusion-transmitted infections. Transfusion 2013; 53: 1088–94.
- 37Ziemann M, Juhl D, Gorg S, et al. The impact of donor cytomegalovirus DNA on transfusion strategies for at-risk patients. Transfusion 2013; 53: 2183–9.
- 38Jordan CT, Saakadze N, Newman JL, et al. Photochemical treatment of platelet concentrates with amotosalen hydrochloride and ultraviolet a light inactivates free and latent cytomegalovirus in a murine transfusion model. Transfusion 2004; 44: 1159–65.
- 39Keil SD, Saakadze N, Bowen R, et al. Riboflavin and ultraviolet light for pathogen reduction of murine cytomegalovirus in blood products. Transfusion 2015; 55: 858–63.
- 40Seed CR, Wong J, Polizzotto MN, et al. The residual risk of transfusion-transmitted cytomegalovirus infection associated with leucodepleted blood components. Vox Sang 2015; 109: 11–7.
- 41MacPherson H. Pragmatic clinical trials. Complement Ther Med 2004; 12: 136–40.
- 42Luce BR, Kramer JM, Goodman SN, et al. Rethinking randomized clinical trials for comparative effectiveness research: the need for transformational change. Ann Intern Med 2009; 151: 206–9.
Citing Literature
Article Metrics
Citations (CrossRef):
34When publishers deposit their content metadata to CrossRef, article citations are tracked and linked, allowing you to see how many times each article has been cited.
Altmetrics:
Scite metrics
Scite uses AI to classify citations by whether they support, contradict, or merely mention the referenced claims.
Explore this article's citation statements on scite.ai
Share QR Code
Generating QR code
QR code copied to clipboard!
Something went wrong while generating your QR code. Please try again in a moment. If the issue persists, refresh the page or contact support.
Export citation

Unable to load citation data. Please try again in a moment.
How to cite
AABB, Clinical Transfusion Medicine Committee, Heddle, N.M., Boeckh, M., Grossman, B., Jacobson, J., Kleinman, S., Tobian, A.A.R., Webert, K., Wong, E.C.C. and Roback, J.D. (2016), AABB Committee Report: reducing transfusion-transmitted cytomegalovirus infections. Transfusion, 56: 1581-1587. https://doi.org/10.1111/trf.13503
Download Citation
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click on download.
This feature enables you to download the bibliographic information (also called citation data, header data, or metadata) for the articles on our site.
Citation manager file format
Use the dropdown list to choose how to format the bibliographic data you're harvesting. Several citation manager formats are available, including EndNote and BibTex. You can then copy the formatted citation (as displayed) or download it as file, to your device. If the RefWorks format is chosen, the 'Download' button will be replaced with an option to directly export to RefWorks




