Primary Nodal Epstein-Barr Virus-Positive T-Cell/NK-Cell Lymphoma: Real-World Experience

Primary nodal Epstein-Barr virus-positive T-cell/NK-cell lymphoma (PTCL-EBV) is a disease entity newly recognized in the World Health Organization's classification of hematolymphoid tumors, 5th edition (WHO-HAEMS5) and the International Consensus Classification of Mature Lymphoid Neoplasms (ICC). Previously, it was classified as a subtype within peripheral T-cell lymphoma, not otherwise specified, and was known to have a poor prognosis. However, the clinical features and treatment outcomes are not well known.

This retrospective observational study was conducted on patients diagnosed with PTCL-EBV at Samsung Medical Center through a pathology review from 2000 to 2020. We analyzed the clinical data from 14 patients, immunohistochemistry, and survival outcomes including overall survival (OS) and progression-free survival (PFS) for each treatment regimen. PFS was defined as the time from the start of chemotherapy to the confirmation of disease progression on imaging, and hematopoietic stem-cell transplantation (HSCT) was considered a consolidation treatment. OS was defined as the time from diagnosis to the time of death.

25% (1 out of 4) were beta-F1 positive, and 67% (4 out of 6) were T-cell receptor gamma (TCRγ) positive. T-cell intracellular antigen (TIA-1) and granzyme B exhibited positive results in all cases (3 out of 3), whereas the NK-cell marker CD56 was positive in only 11% of patients (1 out of 9). CD3 was observed in all of the patients (11 out of 11). The CD4 was 43% positive (3 out of 7). The CD8 was investigated in 8 patients, with 37.5% positive (3 out of 8). Hepatosplenomegaly was observed in 55% of patients (6 out of 11), and 70% (7 out of 10) of patients displayed B symptoms at the time of diagnosis. Patients who received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or CVP (cyclophosphamide, vincristine, prednisolone) treatment had a median PFS of 2.2 months (95% CI: 1.9-2.5 months), and patients who received other treatments had a median PFS of 5.1 months (NA). The objective response rate (ORR) for ICE/dexa (ifosfamide, carboplatin, etoposide, dexamethasone) as the first- or second-line treatment was 100% (3 out of 3). But ORR of CHOP or CVP as the first-line treatment was 33.3% (3 out of 9). The median OS for the group that received HSCT (3 out of 11) after achieving a response was 34.6 months (95% CI: 0-74.6 months), and the median OS for the group that did not receive HSCT (8 out of 11) was 5.0 months (95% CI: 2.1-7.9 months) (p = 0.04).

In conclusion, in the context of PTCL-EBV, despite a limited sample size, the ICE/Dexa regimen shows potential benefits in terms of ORR and PFS. Furthermore, the application of HSCT following the attainment of a complete response may prove advantageous.