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. 2019 Feb 23;219(6):898-907.
doi: 10.1093/infdis/jiy592.

The Ability of a Cytomegalovirus ELISPOT Assay to Predict Outcome of Low-Level CMV Reactivation in Hematopoietic Cell Transplant Recipients

Lynn El Haddad  1 , Ella Ariza-Heredia  1 , Dimpy P Shah  1 , Ying Jiang  1 , Ted Blanchard  2 , Shashank S Ghantoji  1 , Firas El Chaer  1 , Danielle El-Haddad  1 , Amrita Prayag  1 , Lior Nesher  1 , Katy Rezvani  3 , Elizabeth Shpall  3 , Roy F Chemaly  1
Affiliations

The Ability of a Cytomegalovirus ELISPOT Assay to Predict Outcome of Low-Level CMV Reactivation in Hematopoietic Cell Transplant Recipients

Lynn El Haddad et al. J Infect Dis. .

Abstract

Background: Cytomegalovirus (CMV) infections in hematopoietic cell transplant (HCT) recipients cause substantial morbidity and mortality. CMV cell-mediated immunity (CMV-CMI) can be determined by levels of interferon gamma (IFN-γ) production using an enzyme-linked immunospot (ELISPOT) CMV assay (T-SPOT.CMV assay). In this study, we evaluated the ability of this assay to predict the outcome of low-level CMV reactivation in HCT recipients.

Methods: We followed 55 HCT recipients with low-level CMV reactivation up to 8 weeks from enrollment. Progression to clinically significant CMV infection (CS-CMVi) was defined as a CMV load >1000 IU/mL or > 500 IU/mL in patients receiving matched related/autologous or matched unrelated transplants, respectively, and initiation of antiviral treatment.

Results: Progression to CS-CMVi occurred in 31 (56%) of the HCT recipients. Spot counts of CMV-specific pp65 and IE1 antigens were significantly lower in patients who had CS-CMVi than in patients who did not. On multivariate analysis, the ELISPOT CMV responses and steroids use were the only predictors of progression to CS-CMVi.

Conclusions: A strong association between low CMV-CMI and progression to CS-CMVi was observed in HCT recipients. The implementation of serial monitoring of CMV-CMI may identify patients at risk of progression to CS-CMVi that require antiviral therapy.

Keywords: ELISPOT assay; cell-mediated immunity; cytomegalovirus; hematopoietic stem cell transplant; low-level CMV reactivation.

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Figures

Figure 1.
Figure 1.
Flow diagram for patients’ enrollment and cytomegalovirus (CMV) progression.
Figure 2.
Figure 2.
Scatterplots for CMV reactivation versus the number of spots produced in the ELISPOT CMV assay for pp65 (A) and IE1 (B) antigens at various time points. The reference lines at 100 SPC per 250000 cells (A) and at 50 SPC per 250000 cells (B) denote the study-specific thresholds. Note: Patients with CMV disease were not included in this figure. Abbreviations: CMV, cytomegalovirus; ELISPOT, enzyme-linked immunospot; IE1, immediate-early protein 1; pp65, phosphoprotein 65; SPC, spot count.
Figure 3.
Figure 3.
Changes in the median of pp65 SPC (A) and IE1 SPC (B) (both expressed as SPC per 250000 cells), and CMV load (expressed in international units per milliliter) over the 8-week study period in patients with or without CMV events. Abbreviations: CMV, cytomegalovirus; IE1, immediate-early protein 1; PCR, polymerase chain reaction; pp65, phosphoprotein 65; SPC, spot count.
Figure 4.
Figure 4.
Cumulative incidence curves of time to clinically significant CMV infection using the Simon and Makuch method, stratified by high (dashed lines) and low responses to the ELISPOT CMV assay. Note: CMV-CMI level (low /high) was a time-dependent variable in the cumulative incidence curves as it changed over time during the study period. Abbreviations: CMV, cytomegalovirus; CMV-CMI, cytomegalovirus cell mediated immunity; ELISPOT, enzyme-linked immunospot.
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References

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