QuantiFERON®-CMV for Immune-Monitoring in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Background: CMV infection represents a major complication of allo-SCT affecting transplant related mortality and morbidity. Anti-viral therapy is toxic and prolonged treatment could affect graft function. Monitoring specific immune response against CMV could optimize the timing for anti-viral therapy administration in order to avoid related toxicity and to reduce CMV related mortality and morbidity. A recent ELISA based test (QuantiFERON®-CMV) could measure specific (anti-HCMV) and aspecific production of IFN-γ in whole blood.

Aims: to test the reliability of QuantiFERON®-CMV in a cross sectional study in order to identify patients at risk of CMV disease after alloHSCT.

Methods: QuantiFERON^®-CMV is an in vitro diagnostic test using a peptide cocktail simulating human cytomegalovirus proteins (CMV) to stimulate cells in heparinised whole blood. Detection of interferon-γ (IFN-γ) by ELISA is used to identify in vitro responses to these peptide antigens that are associated with CMV infection. The IFN-γ response in the CMV Ag tube is considered positive if > 0.2 UI/mL as defined by the manufacturer. The mitogen-stimulated plasma sample was used as an IFN-γ positive control (PC) for each specimen tested. CMV reactivation and disease were defined according EBMT recommendations.

Results: Among 92 tests no correlation between pp65 antigenemia and IFN-γ production was proved (p=0,346). However, among the 41 tests showing lower levels of anti-HCMV IFN-γ production (<0.2 IU/mL) 8 tests belonging 4 patients were associated with CMV disease, whereas among the 51 tests showing higher levels of anti-HCMV IFN-γ production (>=0.2 IU/mL) none were associated with CMV disease (p=0.001), RR 2.5 (CI95% 1.951–3.321).

Conclusions: QuantiFERON®-CMV doesn’t seem to represent a significant reliable test for risk of viremia after alloHSCT, but patients with prolonged lower levels of anti-HCMV IFN-γ production (<0.2 IU/mL) are at risk of CMV disease. Prospective studies are required in order to identify the correlation between viremia and the need for treatment.