Roy F Chemaly1, Lynn El Haddad1, Drew J Winston2, Scott D Rowley3, Kathleen M Mulane4, Pranatharthi Chandrasekar5, Robin K Avery6, Parameswaran Hari7, Karl S Peggs8, Deepali Kumar9, Rajneesh Nath10, Per Ljungman11, Sherif B Mossad12, Sanjeet S Dadwal13, Ted Blanchard14, Dimpy P Shah15, Ying Jiang1, Ella Ariza-Heredia1. 1. Department of Infectious Diseases, Infection Control, and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 2. Ronald Reagan UCLA Medical Center, Los Angeles, California, USA. 3. Hackensack University Medical Center, New Jersey, USA. 4. Department of Medicine, University of Chicago, Chicago, Illinois, USA. 5. Division of Infectious Diseases, Department of Medicine, Wayne State University, Detroit, Michigan, USA. 6. Division of Infectious Diseases (Transplant Oncology), Johns Hopkins University, Baltimore, Maryland, USA. 7. Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. 8. Department of Haematology, University College London Cancer Institute and University College London Hospitals National Health Service Foundation Trust, London, United Kingdom. 9. Transplant Infectious Diseases, University Health Network, Toronto, Ontario, Canada. 10. Bone Marrow Transplant, Banner MD Anderson Cancer Center, Gilbert, Arizona, USA. 11. Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden. 12. Department of Infectious Diseases, Respiratory Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA. 13. Division of Infectious Diseases, City of Hope, Duarte, California, USA. 14. Oxford Immunotec USA, Inc, Charlotte, North Carolina, USA. 15. Department of Epidemiology and Biostatistics, University of Texas Health, San Antonio, Texas, USA.
Abstract
BACKGROUND: Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. CMV cell-mediated immunity (CMV-CMI) as determined by a peptide-based enzyme-linked immunospot (ELISPOT) CMV assay may identify patients at risk for clinically significant CMV infection (CS-CMVi). METHODS: The CS-CMVi was defined as CMV viremia and/or disease necessitating antiviral therapy. CMV-CMI was characterized as high when the intermediate-early 1 (IE-1) antigen spot counts (SPCs) were >100 (cutoff 1) or when the IE-1 and phosphoprotein 65 antigen SPCs were both >100 SPCs per 250 000 cells (cutoff 2), and a low CMV-CMI when SPCs were below these thresholds. In this prospective multicenter study, we evaluated CMV-CMI every 2 weeks from the pretransplant period until 6 months posttransplantation in 241 allo-HCT recipients with positive CMV serostatus. The primary endpoint was CS-CMVi occurring within 2 weeks of the last measurement of CMV-CMI. RESULTS: CS-CMVi occurred in 70 allo-HCT recipients (29%). CMV-CMI was low in patients who experienced CS-CMVi (94%), whereas those who had a high CMV-CMI were less likely to have CS-CMVi (P < .0001). Patients with CS-CMVi had higher all-cause mortality (P = .007), especially those with low CMV-CMI (P = .035). On multivariable analysis, CMV-CMI, sex, race, antithymocyte globulin, and steroid use were independent predictors of CS-CMVi, and the time from transplant to engraftment was the only predictor of mortality. CONCLUSIONS: Measurement of CMV-CMI using a novel ELISPOT assay would be useful clinically to monitor allo-HCT recipients and distinguish between those at risk of developing CS-CMVi and requiring antiviral prophylaxis or therapy and those who are protected.
BACKGROUND:Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. CMV cell-mediated immunity (CMV-CMI) as determined by a peptide-based enzyme-linked immunospot (ELISPOT) CMV assay may identify patients at risk for clinically significant CMV infection (CS-CMVi). METHODS: The CS-CMVi was defined as CMV viremia and/or disease necessitating antiviral therapy. CMV-CMI was characterized as high when the intermediate-early 1 (IE-1) antigen spot counts (SPCs) were >100 (cutoff 1) or when the IE-1 and phosphoprotein 65 antigen SPCs were both >100 SPCs per 250 000 cells (cutoff 2), and a low CMV-CMI when SPCs were below these thresholds. In this prospective multicenter study, we evaluated CMV-CMI every 2 weeks from the pretransplant period until 6 months posttransplantation in 241 allo-HCT recipients with positive CMV serostatus. The primary endpoint was CS-CMVi occurring within 2 weeks of the last measurement of CMV-CMI. RESULTS:CS-CMVi occurred in 70 allo-HCT recipients (29%). CMV-CMI was low in patients who experienced CS-CMVi (94%), whereas those who had a high CMV-CMI were less likely to have CS-CMVi (P < .0001). Patients with CS-CMVi had higher all-cause mortality (P = .007), especially those with low CMV-CMI (P = .035). On multivariable analysis, CMV-CMI, sex, race, antithymocyte globulin, and steroid use were independent predictors of CS-CMVi, and the time from transplant to engraftment was the only predictor of mortality. CONCLUSIONS: Measurement of CMV-CMI using a novel ELISPOT assay would be useful clinically to monitor allo-HCT recipients and distinguish between those at risk of developing CS-CMVi and requiring antiviral prophylaxis or therapy and those who are protected.
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