T-cell large granular lymphocytic leukemia (LGL) is a rare type of T-cell lymphomas characterized by proliferation of clonal LGL (in the amount exceeding 0.5 x 109/L) that generally have CD3+, CD8+, CD16+, CD57+, CD5+ and/or CD7+, TCRαβ+, TIA1+, granzyme B+ phenotype, as well as by chronic benign clinical course (median overall survival is >10 years). So far, first-line therapy for the disease (if it is clinically indicated, i.e. in case of anemia - hemoglobin concentration <100 g/L, thrombocytopenia <50х109/L, neutropenia <0.5х109/L, splenomegaly, recurrent infections, autoimmune disorders, B-symptoms) has not been established.
The goal of the study: to evaluate clinical and immunophenotyping characteristics, hematological parameters and the results of initiating therapy in a large patient cohort.
Forty-nine patients with verified T-LGL diagnosis were enrolled in the study based on the results of immunophenotyping and molecular genetic testing.
Results: Our study showed that T-cell large granular lymphocytic leukemia was more often diagnosed in females (M:F=1:1.3) with the median age of 52 years. The results of the clinical data analysis were as follows: cytopenia affecting two lineages was observed in 51% of the patients (33% - anemia; 18% - thrombocytopenia); histologically confirmed bone marrow infiltration was revealed in 24% of patients; splenomegaly - in 31% of patients. Specific febrile fever, night sweats, weight loss (B-symptoms), frequently recurrent infectious complications were registered in 31% of patients. Diagnostically confirmed autoimmune disorders (rheumatoid arthritis etc.) were revealed only in 8% of cases.
The immunophenotyping features of the tumor cells were as follows: CD3+ (in 59% of patients), CD8>CD4 (55%), CD4>CD8 (8%), TCRab+ (51%), TCRgd+ (35%), CD16CD56+ (45%), while double-negative profile (CD4-CD8) was revealed in 8% of cases.
25 of 49 patients (51%) did not have indications for treatment initiation and were followed up. In other patients who required therapy initiation, the distribution of treatment options was as follows: low-dose methotrexate was used in 21% (80% demonstrated progressive disease/no response to therapy), cyclophosphamide (100 mg/day) - in 33% (CR was achieved in 50% of patients), cyclosporine A - in 8% (disease progression in all cases) cases, respectively; and 54% of patients received immune therapy with interferon alfa-containing drugs (CR and PR were achieved in 42% and 24% of patients, respectively). Median follow-up time in patients who received first-line therapy was 16.5 months.
Conclusions: our retrospective study conducted in a large patient cohort showed that the disease was most often prevalent clinical signs being B-symptoms, recurrent infectious complications, anemia and anemia-related syndrome. 50% of patients did not require the initiation of specific therapy. It is the first study evaluating the use of immune therapy with interferon-alfa-containing drugs as a first-line therapy for the disease, which has demonstrated good and promising results (general response was achieved in 66% of patients).
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.