Development of T-cell large granular lymphocytic leukemia in the course of B-cell chronic lymphocytic leukemia with a causal relationship inferred from a flow cytometric analysis of the bone marrow aspirate

Background: B-cell chronic lymphocytic leukemia is the most frequent leukemia in the western world while T-cell large granular lymphocytic leukemia with cytotoxic (CD8+/CD3+CD4-) immunophenotype is rare. There is much ongoing interest regarding the interaction between T cells and B-cell chronic lymphocytic leukemia cells. Methods: Peripheral blood and bone marrow samples from a 72 year-old-man with a simultaneous presence of these two types of leukemia were examined and analyzed by conventional morphology, flow cytometry, immunohistochemistry, chromosomal study, and molecular studies. Results: Flow cytometric analysis of the bone marrow aspirate documented B-cell chronic lymphocytic leukemia, CD3+ CD8+ T-cell large granular lymphocytic leukemia, and demonstrated the presence of three subpopulations of CD8+ T-cells with transitional immunophenotypes between that of benign and malignant CD8+ T-cells. Conclusions: We report the first case of simultaneous presence of B-cell chronic lymphocytic leukemia and T-cell large granular lymphocytic leukemia with cytotoxic (CD8+/CD3+/CD4-) immunophenotype. The simultaneous presence of malignant CD8+CD3+ T-cell large granular lymphocytes together with the three immunophenotypically different subpopulations of CD3+ CD8+ T-cells indicated an ongoing stepwise malignant transformation of large granular lymphocytes late in the 9-year-course of B-cell chronic lymphocytic leukemia. We propose that chronic antigenic stimulation by B-cell chronic lymphocytic leukemia cells and immune deficiency inherent to B-cell chronic lymphocytic leukemia additionally augmented by treatment with fludarabine, may cause development of T-cell large granular lymphocytic leukemia.