Probability of CMV infection
| . | CMV reactivation (any DNAemia) . | Clinically significant CMV . | ||||||
|---|---|---|---|---|---|---|---|---|
| Variable . | HR . | Lower . | Upper . | P . | HR . | Lower . | Upper . | P . |
| Univariate analysis | ||||||||
| Unrelated donor* | 2.16 | 0.72 | 6.47 | .17 | 10.1 | 1.21 | 83.6 | .03 |
| Lymphoid malignancy | 0.22 | 0.03 | 1.72 | .15 | 1.5 | 0.29 | 7.66 | .64 |
| CMV seronegative donor | 0.56 | 0.18 | 1.73 | .32 | 2.4 | 0.29 | 19.9 | .42 |
| Steroids† | 0.58 | 0.05 | 6.88 | .67 | 2.94 | 0.4 | 21.8 | .29 |
| IL-2+IFN-γ+TNF-α+MIP-1β+ CD8+ T cells‡ (PS) | 1.89 | 0.58 | 6.16 | .29 | 0.26 | 0.06 | 1.14 | .07 |
| IL-2−IFN-γ+TNF-α−MIP-1β+ CD8+ T cells§ (NPS) | 8.15 | 1.1 | 62.9 | .04 | 7.16 | 0.86 | 59.5 | .07 |
| Composite biomarker‖ | 1.34 | 0.41 | 4.37 | .63 | 6.92 | 1.44 | 31.1 | .01 |
| . | CMV reactivation (any DNAemia) . | Clinically significant CMV . | ||||||
|---|---|---|---|---|---|---|---|---|
| Variable . | HR . | Lower . | Upper . | P . | HR . | Lower . | Upper . | P . |
| Univariate analysis | ||||||||
| Unrelated donor* | 2.16 | 0.72 | 6.47 | .17 | 10.1 | 1.21 | 83.6 | .03 |
| Lymphoid malignancy | 0.22 | 0.03 | 1.72 | .15 | 1.5 | 0.29 | 7.66 | .64 |
| CMV seronegative donor | 0.56 | 0.18 | 1.73 | .32 | 2.4 | 0.29 | 19.9 | .42 |
| Steroids† | 0.58 | 0.05 | 6.88 | .67 | 2.94 | 0.4 | 21.8 | .29 |
| IL-2+IFN-γ+TNF-α+MIP-1β+ CD8+ T cells‡ (PS) | 1.89 | 0.58 | 6.16 | .29 | 0.26 | 0.06 | 1.14 | .07 |
| IL-2−IFN-γ+TNF-α−MIP-1β+ CD8+ T cells§ (NPS) | 8.15 | 1.1 | 62.9 | .04 | 7.16 | 0.86 | 59.5 | .07 |
| Composite biomarker‖ | 1.34 | 0.41 | 4.37 | .63 | 6.92 | 1.44 | 31.1 | .01 |
| Variable . | aHR . | Lower . | Upper . | P . | aHR . | Lower . | Upper . | P . |
|---|---|---|---|---|---|---|---|---|
| Multivariate analysis | ||||||||
| Unrelated donor* | 3.3 | 1.04 | 10.3 | .04 | 7.9 | 0.93 | 66.6 | .06 |
| IL-2−IFN-γ+TNF-α−MIP-1β+ CD8+ T cells§ (NPS) | 10.9 | 1.4 | 87.5 | .02 | ||||
| Composite biomarker‖ | 5.1 | 1.12 | 23.1 | .04 | ||||
| Multivariate analysis 2 | ||||||||
| Steroids† | 0.39 | 0.03 | 4.41 | .45 | 3.61 | 0.41 | 31.7 | .25 |
| IL-2−IFN-γ+TNF-α−MIP-1β+ CD8+ T cells§ (NPS) | 8.97 | 1.15 | 69.7 | .04 | ||||
| Composite biomarker‖ | 5.42 | 1.18 | 24.8 | .03 |
| Variable . | aHR . | Lower . | Upper . | P . | aHR . | Lower . | Upper . | P . |
|---|---|---|---|---|---|---|---|---|
| Multivariate analysis | ||||||||
| Unrelated donor* | 3.3 | 1.04 | 10.3 | .04 | 7.9 | 0.93 | 66.6 | .06 |
| IL-2−IFN-γ+TNF-α−MIP-1β+ CD8+ T cells§ (NPS) | 10.9 | 1.4 | 87.5 | .02 | ||||
| Composite biomarker‖ | 5.1 | 1.12 | 23.1 | .04 | ||||
| Multivariate analysis 2 | ||||||||
| Steroids† | 0.39 | 0.03 | 4.41 | .45 | 3.61 | 0.41 | 31.7 | .25 |
| IL-2−IFN-γ+TNF-α−MIP-1β+ CD8+ T cells§ (NPS) | 8.97 | 1.15 | 69.7 | .04 | ||||
| Composite biomarker‖ | 5.42 | 1.18 | 24.8 | .03 |
aGVHD grade 2 to 4 was not included as a predictor in this analysis because CMV DNAemia preceded the onset of aGVHD in all cases. Statistically significant P values (P < .05) are indicated in bold.
aHR, adjusted hazard ratio; HR, hazard ratio.
All unrelated donor recipients at our center undergo T-cell depletion with ATG during the conditioning regimen. Typical dose of ATG at our center is 4 mg/kg total.
Prednisone >0.5mg/kg per day prior to day +30.
Based on CD8+ T-cell responses to CMV-pp65 measured on day +30. High levels of PS were defined as >1.5% for CMV reactivation (any DNAemia), and as >0.45% for clinical significant CMV reactivation.
Based on CD8+ T-cell responses to CMV-pp65 measured on day +30. High levels of NPS were defined as >5.7% for CMV reactivation (any DNAemia), and as >16% for clinical significant CMV reactivation.
Composite biomarker consisted of low levels of the PS (IL-2+IFN-γ+TNF-α+MIP-1β+) and NPS high levels of the (IL-2−IFN-γ+TNF-α−MIP-1β+) NPS using cutoff outlined above.