Large granular lymphocyte leukemia and natural killer cell leukemia/lymphomas

Natural killer (NK) cell leukemia and lymphoma represent rare conditions with heterogeneity of biologic behavior, prognosis, and responsiveness to therapy. The initial diagnosis of NK-cell malignancies can be difficult because of the lack of immunophenotypic clonality markers, morphologic heterogeneity, and a poor correlation between cytomorphology and prognosis. Therapeutic recommendations for NK-cell malignancies are derived from retrospective studies or case reports. Immature NK-cell malignancies often have aggressive behavior with poor prognosis, despite administration of acute myeloid leukemia or acute lymphocytic leukemia induction chemotherapy. The use of high-dose chemotherapy with stem cell rescue resulted in a prolonged survival in a small series of patients. NK-cell malignancies originating from cells with mature phenotypes form a spectrum of diseases with distinct prognosis. Patients with aggressive NK-cell leukemia invariably die within several months. Nasal and nasal-like NK/T-cell lymphomas with limited stage disease often respond to radiation therapy alone or combination with chemotherapy and radiation therapy, with 5-year disease-free survival rates ranging from 30% to 75%. Patients with T-cell large granular lymphocyte leukemia or chronic NK-cell lymphoproliferative disease of granular lymphocytes can have an indolent clinical course with long survival without therapy. However, approximately 66% of patients with T-cell large granular lymphocyte leukemia require low-dose chemotherapy with methotrexate or cyclophosphamide or immunosuppressive therapy with glucocorticosteroids or cyclosporine A for symptomatic cytopenias during the course of their disease.