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

Abstract

Background: CMV-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.

Objectives: We 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 design: CMV pp65 and IE1-specific ELISPOT assays were performed before HCT (D0), and at 30 (D30) and 90 (D90) days after HCT.

Results: Of 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).

Conclusion: Dynamic change in the CMV-specific ELISPOT assay before versus after HCT appears to predict the subsequent development of CMV infection and relapsing CMV infection.

Keywords: Cytomegalovirus; ELISPOT; Hematopoietic stem cell transplantation.