Absolute Lymphocyte Count: A Predictor of Recurrent Cytomegalovirus Disease in Solid Organ Transplant Recipients

Abstract

Background: Recurrent cytomegalovirus (CMV) disease in solid organ transplant recipients frequently occurs despite effective antiviral therapy. We previously demonstrated that patients with lymphopenia before liver transplantation are more likely to develop posttransplant infectious complications including CMV. The aim of this study was to explore absolute lymphocyte count (ALC) as a predictor of relapse following treatment for CMV disease.

Methods: We performed a retrospective cohort study of heart, liver, and kidney transplant recipients treated for an episode of CMV disease. Our primary outcome was time to relapse of CMV within 6 months. Data on potential predictors of relapse including ALC were collected at the time of CMV treatment completion. Univariate and multivariate hazard ratios (HRs) were calculated with a Cox model. Multiple imputation was used to complete the data.

Results: Relapse occurred in 33 of 170 participants (19.4%). Mean ALC in relapse-free patients was 1.08 ± 0.69 vs 0.73 ± 0.42 × 103 cells/μL in those who relapsed, corresponding to an unadjusted hazard ratio of 1.11 (95% confidence interval, 1.03-1.21; P = .009, n = 133) for every decrease of 100 cells/μL. After adjusting for potential confounders, the association between ALC and relapse remained significant (HR, 1.11 [1.03-1.20]; P = .009).

Conclusions: Low ALC at the time of CMV treatment completion was a strong independent predictor for recurrent CMV disease. This finding is biologically plausible given the known importance of T-cell immunity in maintaining CMV latency. Future studies should consider this inexpensive, readily available marker of host immunity.

Figures

Figure 1.

Unadjusted Kaplan-Meier estimates of relapse-free survival stratified by recipient cytomegalovirus (CMV) serostatus at the time of transplantation (A), receipt of antilymphocyte therapy (ALT) within 1 year prior to the completion of CMV treatment (B), and peak viral load (VL) (C). P values refer to log-rank test results (n = 170).

Figure 2.

Distribution of absolute lymphocyte counts at time of cytomegalovirus (CMV) treatment completion in patients who did (n = 29) and did not (n = 104) experience CMV relapse.

Figure 3.

Unadjusted Kaplan-Meier estimates of relapse-free survival stratified by absolute lymphocyte count (×1000 cells/μL) at the time of treatment completion (n = 133). Hazard ratios (HRs) for relapse for each strata with 95% confidence intervals are displayed.