The Ability of a Cytomegalovirus ELISPOT Assay to Predict Outcome of Low-Level CMV Reactivation in Hematopoietic Cell Transplant Recipients

• Published in: The Journal of infectious diseases 2019-02, Vol.219 (6), p.898-907
• Main Authors: El Haddad, Lynn, Ariza-Heredia, Ella, Shah, Dimpy P, Jiang, Ying, Blanchard, Ted, Ghantoji, Shashank S, El Chaer, Firas, El-Haddad, Danielle, Prayag, Amrita, Nesher, Lior, Rezvani, Katy, Shpall, Elizabeth, Chemaly, Roy F
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antigens; Antigens, Viral - immunology; Antiviral agents; Antiviral Agents - therapeutic use; Antiviral drugs; Autografts; Biomarkers - blood; Cell-mediated immunity; Cohort Studies; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus - physiology; Cytomegalovirus Infections - diagnosis; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - virology; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunospot Assay; Female; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; IE1 protein; Immunity, Cellular; Interferon-gamma - blood; Major and Brief Reports; Male; Middle Aged; Morbidity; Multivariate analysis; Pp65 protein; Prospective Studies; Stem cell transplantation; Steroid hormones; Transplant Recipients; Transplants & implants; Viral Load; Virus Activation; γ-Interferon
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiy592

Most patients with high CMV-CMI and low-level CMV reactivation did not progress to clinically significant CMV infection. Low CMV-CMI and steroids use were the only predictors for CMV progression from low-level reactivation. Abstract Background Cytomegalovirus (CMV) infections in hematopoietic cell transplant (HCT) recipients cause substantial morbidity and mortality. CMV cell-mediated immunity (CMV-CMI) can be determined by levels of interferon gamma (IFN-γ) production using an enzyme-linked immunospot (ELISPOT) CMV assay (T-SPOT.CMV assay). In this study, we evaluated the ability of this assay to predict the outcome of low-level CMV reactivation in HCT recipients. Methods We followed 55 HCT recipients with low-level CMV reactivation up to 8 weeks from enrollment. Progression to clinically significant CMV infection (CS-CMVi) was defined as a CMV load >1000 IU/mL or > 500 IU/mL in patients receiving matched related/autologous or matched unrelated transplants, respectively, and initiation of antiviral treatment. Results Progression to CS-CMVi occurred in 31 (56%) of the HCT recipients. Spot counts of CMV-specific pp65 and IE1 antigens were significantly lower in patients who had CS-CMVi than in patients who did not. On multivariate analysis, the ELISPOT CMV responses and steroids use were the only predictors of progression to CS-CMVi. Conclusions A strong association between low CMV-CMI and progression to CS-CMVi was observed in HCT recipients. The implementation of serial monitoring of CMV-CMI may identify patients at risk of progression to CS-CMVi that require antiviral therapy.