High Rates of HTLV-1 Seropositivity in Patients with EBV-Positive Diffuse Large B-Cell Lymphoma

Background: Epstein-Barr virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) of the elderly is a novel entity included in the most recent edition of WHO Classification of hematologic neoplasms. It usually affects patients older than 60 years of age and carries a poor survival. Human T-lymphotrophic virus type 1 (HTLV-1) is a retrovirus that induces immunosuppression, has been associated with the development of adult T-cell leukemia/lymphoma, and has a high prevalence in Peruvian population.

Aim: The goal of this retrospective study was to evaluate the HTLV-1 serological status in EBV-positive DLBCL Peruvian patients.

Methods: We identified untreated patients with a diagnosis of DLBCL between January 2002 and June 2015 from the medical records of our institution. IRB approval was obtained prior to data collection. HTLV-1 positivity was defined based on Western Blot analysis. EBV-positivity was defined by identifying at least 10% EBV-encoded RNA (EBER) expression by chromogenic in situ hybridization in the pathological sample. Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the immunohistochemical expression of CD20, PAX5, BCL6, CD10, CD30 and MUM-1/IRF4 for re-classification purposes.

Results: A total of 210 patients with DLBCL were identified. Of these, 11 patients (5%) were HTLV-1 seropositive and 199 (95%) were HTLV-1 seronegative. Thirty-two patients (15%) were EBV-positive by expression of EBER and 178 (85%) were EBV-negative. HTLV-1 positivity was found in 4/32 (12.5%) of EBV-positive DLBCL patients, and in 7/178 (4%). The odds ratio for HTLV-1 positivity in EBV-positive DLBCL was 3.5 (95% CI 0.7-14.7; p=0.045) when compared with the EBV-negative group. The median age of the HTLV-1-positive DLBCL patients was 65 years (range 45-85 years). There were 5 (45%) men and 6 women (55%). ECOG was >1 in 5 patients (45%), LDH was elevated in 8 (73%), extranodal disease in 7 (64%), and advanced clinical stage (III and IV) in 7 (64%). High IPI score (3-5 factors present) was seen in 8 patients (73%). Interestingly, all the patients who were EBV-positive and HTLV-1-positive presented with early stage (I and II), normal LDH levels and low IPI scores (0-2 factors).

Conclusions: There is a high prevalence of HTLV-1 seropositive status in patients with EBV-positive DLBCL. Patients with double EBV and HTLV-1 positivity appear to present at earlier stages and with lower risk disease. Larger studies are needed to confirm these findings.