Elevated Peripheral Blood (PB) Cytomegalovirus (CMV) Viral Loads and Reduced CD8+ T-Cell Counts Are Common Findings in T-Cell Lymphoma before Initiation of Therapy.

Background. T-cell lymphomas are often associated with abnormal T-cell responses. A viral etiology for certain subsets of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL) has been proposed, but viral isolates from fresh malignant T-cells are rare. Recently, a significant association between cytomegalovirus (CMV) seropositivity and CTCL was observed (

Methods. A total of 56 patients with either CTCL (n=41) or PTCL (n=15) were assayed for whole blood quantitative CMV viral loads using a hybrid capture assay for CMV DNA (Digene). PB immunophenotyping by flow cytometry was used to determine absolute CD8⁺ T-cell counts. In-situ PCR was used to detect CMV DNA in tumor samples.

Results. Only 2/56 patients had symptoms consistent with CMV reactivation at the time of the assay. Elevated CMV viral loads were seen in 15/56 (27%) of patients with a patient/cutoff ratio range of 1.0–107.6 and a median of 1.52 for CTCL and 2.14 for PTCL (>1.0 = positive). While all 15 patients with CMV viremia had positive serology for CMV, only 16/41 patients without elevated CMV viral loads were seropositive for CMV. Thus, although CMV viremia paralleled CMV seropositive status, the overall seroprevalence of CMV in this cohort 31/56 (55.3%) was not significantly different from that of the general population. The absolute CD8⁺ T-cell count was <200/mm³ in 8/15 (53.3%) patients and there was a significant relationship between lower CD8⁺ T-cell counts and higher CMV titers (p<.003). None of the 4 tumor samples tested from patients with elevated CMV viral loads (3 CTCL and 1 PTCL) was positive for CMV DNA.

Conclusions. We found that CMV seroprevalence in this cohort of PTCL and CTCL was not greater than that reported in the general population (55.3%). However, we report a previously undescribed high frequency (27%) of CMV viremia, before systemic therapy, and a significant correlation between higher CMV viral loads and degree of CD8⁺ T-cell lymphopenia. Whether this association reflects a yet to be defined pathogenic role of CMV in T-cell lymphoma or is simply the result of decreased T-cell immunosurveillance remains to be established. The absence of CMV DNA in a limited number of tumor samples from patients with elevated viral load does not support a direct pathogenic role of CMV, although a larger study is needed to confirm this hypothesis. The correlation between lower CD8⁺ T-cells and CMV viral load suggests defective T-cell immunosurveillance against CMV. A prospective quantitative monitoring study of CMV-specific T-cell responses, CMV DNA viral loads and expression in tumor cells from patients with T-cell lymphoma and appropriate controls (normal volunteers and patients with other hematological malignancies) is in development.