A Prospective Observational Study to Evaluate a Cytomegalovirus (CMV)-Specific Enzyme-Linked Immunospot (Elispot) Assay in Allogeneic Hematopoietic Cell Transplant (Allo-HCT) Recipients: The REACT Study
Year: 2017
Type: article
Study design: Observational Study
Abstract: Background: CMV infection causes significant morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). CMV management after HCT includes risk stratification comprised mainly by a preemptive strategy with CMV viral load monitoring. Cell mediated immunity (CMI) plays a role in CMV reactivation through cytokine responses such as T cell production of interferon gamma (IFN-γ). Quantification of CMV CMI may have value in CMV management. This study evaluated the potential role of a CMV-specific ELISPOT assay in allo-HCT recipients within 26 weeks post-HCT. Methods: This is an ongoing, multi-center (13 sites), prospective, observational study of 136 adult CMV seropositive allo-HCT recipients. CMV management was according to institutional protocols. Date of CMV reactivation, as defined by each institution, was recorded. T cell responses were serially monitored pre-, and every 2 weeks post-HCT and up to 26 weeks with an ELISPOT assay that uses CMV-specific antigens IE-1 and pp65 (T-SPOT.CMV, Oxford Diagnostics Laboratories®, Memphis, TN). Data reviewed included patients reaching ≥12 weeks post-HCT as of July 2016. Results: Out of 136 patients, 108 reached 12 weeks and 50 completed the study at 26 weeks. Majority of the 136 patients are white (67%), males (56%), with a median age of 56 (23 – 80) years. Half (50%) had unrelated, while 50 (37%) had matched HCT. Most of the donors (53%) were CMV sero-positive. CMV reactivation occurred in 56 patients (43%) and time to first reactivation occurred at a mean of 5.5 weeks (range: 2-12) post-HCT (Figure 1). This timeframe is consistent with low median CMV specific spot counts and higher non-specific PHA induced spot counts (Figure 2). A comparison of reactivation events with median antigen spot counts demonstrates the inverse relationship between increased CMV specific immune function with protection from CMV reactivation (Figure 3).Figure 2Median T-SPOT response.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3First Reaction vs Median T-SPOT Reconstitution.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusion: An interim analysis of the first 136 patients in the REACT study demonstrates CMV reactivation occurred within 12 weeks following transplantation when the CMV immune response measured by a CMV-specific ELISPOT assay was lower. In contrast, no reactivation was seen later when CMV-specific response was higher. This study suggests insights into the CMV immune response which may guide personalized decisions regarding CMV management.
Authors: Ella J. Ariza-Heredia, Dimpy P. Shah, Drew J. Winston, Scott D. Rowley, Kathleen M. Mullane, Pranatharthi Chandrasekar, Robin K. Avery, Parameswaran Hari, Karl S. Peggs, Deepali Kumar, Rajneesh Nath, Per T. Ljungman, Sherif B. Mossad, Sanjeet S. Dadwal, William Cruikshank, Firas El Chaer, Roy F. Chemaly
Institutions: The University of Texas MD Anderson Cancer Center, University of California, Los Angeles, Los Angeles Medical Center, Hackensack University Medical Center, University of Chicago Medical Center, Wayne State University, The Barbara Ann Karmanos Cancer Institute, Johns Hopkins University, Medical College of Wisconsin, University College London, Toronto General Hospital, University of Massachusetts Chan Medical School, Karolinska University Hospital, Cleveland Clinic, City Of Hope National Medical Center, City of Hope, Oxford Immunotec (United Kingdom)
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2591565301