Background: CMV infection causes significant morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). CMV cell mediated immunity, as assessed by T cells production of interferon gamma (IFN-γ) and other cytokines, is considered as a major pathway to control CMV replication. We aimed to evaluate the ability of a CMV-specific ELISPOT assay to predict the outcome of low-level CMV reactivation in allo-HCT recipients.
Methods: In this prospective observational study, we enrolled allo-HCT recipients with low level of CMV viral loads (VL) <1000 IU/ml or <500 IU/ml if they had graft-versus-host disease or were receiving systemic corticosteroids. Patients were serially monitored with a CMV-specific ELISPOT assay (T-SPOT®.CMV, Oxford Diagnostics Laboratories®, Memphis, TN) on a weekly basis and up to 8 weeks from the date of first CMV reactivation. Progression from low level reactivation was defined as either ≥50% increase in CMV VL and/or CMV end-organ disease. Data from 25 patients who reached 4 weeks of follow-up were analyzed.
Results: Majority of the patients were white (43%), males (70%), with a median age of 58 (18 68) years, and had unrelated (52%) or matched related (30%) HCT. Progression of CMV infection occurred in 12 (52%) allo-HCT recipients. We observed an inverse correlation of peak CMV VL with CMV specific pp65 spot counts (SPC) (Coefficient= -0.44, P = 0.01). Mean (±SD) pp65 SPC was significantly lower in patients who progressed from low level CMV reactivation when compared to patients who did not (10 (± 20) vs. 183 (± 138) SPC; P= 0.0003, respectively). The risk of CMV progression was 52% for a decline of 10 pp65 SPC by next time point of measurement (OR= 1.52 (1.04 2.21), P = 0.029).
Conclusion: Preliminary analyses showed an association between low CMV-specific T cell responses and progression of CMV infection in allo-HCT recipients. Serial monitoring of anti-CMV immune response may help stratify allo-HCT recipients at risk of progression from low CMV VL to significant CMV infection, but needs further validation.
F. El Chaer, None
L. El Haddad, None
D. El-Haddad, None
A. Prayag, None
L. Nesher, None
K. Rezvani, None
E. Shpall, None
R. F. Chemaly, Oxford Immunotec: Consultant , Grant Investigator and Investigator , Consulting fee , Research support and Speaker honorarium