Internal medicine

Virus

Cytomegalovirus

Cytomegalovirus infections

Hematopoietic cell

Cytomegalovirus infection

Biology

Haematopoiesis

Virology

Herpesviridae

Immunology

Hematopoietic stem cell transplantation

Immunity

Betaherpesvirinae

Viral disease

Stem cell

Human cytomegalovirus

Cell mediated immunity

Transplantation

Genetics

Medicine

Immune system

Clinical Infectious Diseases

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 &amp;gt;100 (cutoff 1) or when the IE-1 and phosphoprotein 65 antigen SPCs were both &amp;gt;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 &amp;lt; .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.

Cytomegalovirus (CMV) Cell-Mediated Immunity and CMV Infection After Allogeneic Hematopoietic Cell Transplantation: The REACT Study