Diagnostic usefulness of dynamic changes of CMV-specific T-cell responses in predicting CMV infections in HCT recipients

Abstract

BackgroundCMV-specific cell mediated immune responses before and after hematopoietic stem cell transplantation (HCT) can categorize patients as at high or low risk of CMV development. ObjectivesWe evaluated the usefulness of the CMV-specific T-cell ELISPOT assay for predicting the development of CMV infections after HCT in recipients with donor-positive and recipient-positive CMV serology (D+/R+ ). Study designCMV pp65 and IE1-specific ELISPOT assays were performed before HCT (D0), and at 30 (D30) and 90 (D90) days after HCT. ResultsOf the 84 HCT recipients with D+/R+, 42 (50%) developed≥1 episode of CMV infection. Thirty-nine (64%) of 61 patients with Δ(D30-D0) pp65<42 developed CMV infections compared with 3 (14%) of 21 patients with Δ(D30-D0) pp65≥42 (P<0.001). Twenty-three (74%) of 31 patients with Δ(D30-D0) IE1<−4 developed CMV infections compared with 19 (37%) of 51 patients with Δ(D30-D0) IE1≥−4 (P=0.001). pp65 Δ(D30-D0) ≥42 had 93% sensitivity for ruling out subsequent CMV infection, and pp65 Δ(D30-D0)<42 followed by Δ(D30-D0) IE1<−4 had 100% specificity for ruling in the subsequent CMV infection. In addition, 10 (53%) of 19 patients with Δ(D90-D30) pp65<23 had relapsing CMV infections, compared with 3 (15%) of 20 patients with Δ(D90-D30) pp65≥23 (P=0.02). The sensitivity and specificity of Δ(D90-D30) pp65 were 77% (95% CI 50–92) and 65% (95% CI, 46–81). ConclusionDynamic change in the CMV-specific ELISPOT assay before versus after HCT appears to predict the subsequent development of CMV infection and relapsing CMV infection.