QuantiFERON-CMV Monitoring Post-Allogeneic Hematopoietic Stem Cell Transplantation Is Dynamic and Predictive of...

Immune responses may determine natural history and optimal management of cytomegalovirus (CMV) reactivation following allogeneic hematopoietic cell transplantation (alloHCT). To assess this, we performed serial QuantiFERON-CMV (QFCMV, Qiagen) and QuantiFERON-Monitor (QF-monitor, Qiagen) tests, measuring CMV-specific T cell interferon-γ responses (IFNγ), and stimulators of innate (TLR7) and adaptive immunity (CD3), respectively.

In a prospective multicenter study of adult CMV-seropositive alloHCT recipients, QFCMV and QF-monitor tests were collected serially. Association with CMV outcomes was analyzed using multivariable Cox and mixed effects regression analysis.

Overall, 119 patients had 385 QFCMV tests (median [IQR]:3 [3-4] per patient). csCMVi occurred in 45.4% patients. QFCMV reactivity was achieved in 16% of patients at 6 weeks, 38.3% at 12 weeks, and 40.2% any time during the study. Reactivity was predictive of lower peak CMV viral load in the 6 weeks following testing (-0.41 × log₁₀ [95% CI -0.77 to -0. 04 × log₁₀], p = 0.02), but did not impact csCMVi. Analysis of mitogen-stimulated IFNγ responses within QFCMV testing showed reduced risk of csCMVi in the following 6 weeks (adjusted HR 0.92 [95% CI 0.85-0.99], p = 0.025) and each 1 IU/mL IFNγ increase was associated with decreased peak viral load (-0.02 × log₁₀ [95% CI -0.03 to 0.00 × log₁₀], p = 0.02). QF-monitor was not associated with any CMV outcomes.

QFCMV reactivity was associated with lower peak CMV viral load but not csCMVi. Mitogen-stimulated IFNγ response correlated with csCMVi, suggesting a role for broader assessment of cellular immunity post-transplant. Despite incorporating adaptive immunity measures, QF-monitor was limited in assessing CMV risk. QFCMV reactivity was infrequently achieved in the early post-allogeneic stem cell transplant period. Qualitative QFCMV result was associated with peak CMV viral load but not clinically significant infection, while magnitude of the mitogen response predicted reduction in clinically significant CMV infection.