Clinical and Immunophenotypic Differences of Patients with T/NK-Cell Large Granular Lymphocytic Leukemia

Background: According to the WHO, T/NK-cell large granular lymphocytic leukemia (T/NK-LGL) comprises 2 – 5 % of all T/NK tumors. In addition, T/NK-LGL is a very heterogeneous disease. T/NK-LGL has been divided along 2 basic types: T-cell and NKcell leukemias. We found further differences among these two basic types. Among our patients with T/NK-LGL, there were 5 immunophenotypic variants with differences in severity of their disease and other clinical parameters.

Materials and Methods: Thirty five patients were diagnosed with T/NK-LGL from 01.1998 to 01.2008 (13 men and 22 women) in the age from 18 to 71 years (median age 58 years). The median survival has not been achieved. The median follow up is 72 months. Clinical common features: lymphocytosis in blood and bone marrow, cytopenia (80%), splenomegaly, rheumatoid arthritis and B-symptoms. Unusual features: lymphadenopathy, vasculitis and neuropathy. Diagnostic methods: histology, cytology and flow two-color cytometry with monoclonal antibodies (“Becton Dickinson Immunocytometry Systems” USA and “Dako” Denmark). Clonality was defined by a PCR- on T-cell receptor gene rearrangement.

Results: Twenty six patients: 18 women and 8 men were accurately classified as «T/NK - cellular leukemia - LGL» according to WHO classification. The remaining 9 cases had rare immunophenotypes. All (35) patients were subdivided into 5 groups by immunophenotypic (IFT) features of leukemic lymphocytes. 1^st group (4 women) had the following IFT of the leukemic lymphocytes: CD2⁺CD3⁻CD56^+/−CD16⁺. In the 2^d group, 9 patients (5 men and 4 women) had IFT of CD2+CD3+CD8+CD16+CD56^+/−. There were 13 patients (3 men and 10 women) in the 3^d group. Variant of IFT with leukemic T-cells was CD3⁺CD8⁺CD16⁻CD56⁻. There were 5 patients (2 men and 3 women) in the 4^th group. 20–60 % peripheral blood lymphocytes simultaneous expressed CD8 and CD4 (double – positive T-cells). Others had 40–20% lymphocytes expressing only CD8⁺ marker. In the 5^th group, there were 4 patients (2 men and 2 women). The pathologic T-cells were detected only on the bone marrow aspirate. There had heavy bone marrow aplasia or predominantly red cell aplasia. IFT of lymphocytes in the bone marrow was aberrant with presence of some markers of T-cells, including, CD8, absence of CD16 and CD56. The first three groups appeared stable and did not require chemotherapy for prolonged time (11 of 26 patients, overall 42%). A median of follow-up without treatment is 70 months. The patients of 4^th and 5^th group required immediate intervention and were treated with chemotherapy.

Conclusions: Immunohistochemical characteristics of T-cells separate T/NK-LGL patients with stable disease from those that present with cytopenias and require immediate intervention. The molecular characteristics of these cells will be further defined.