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HEMATOPOIESIS IN PATIENTS WITH ACUTE NATURAL KILLER CELL LEUKEMIA AND LARGE GRANULAR LYMPHOCYTOSIS: RELATIONSHIP BETWEEN CLINICAL FEATURES AND HEMATOPOIETIC INHIBITOR ACTIVITY OF PERIPHERAL MONONUCLEAR CELLS

Large granular lymphocytosis is characterized by a remarkable increase of large granular lymphocytes (LGL) with azurophilic granules in the cytoplasma, and about two-thirds of patients with LGL lymphocytosis do not show severe neutropenia, anemia and thrombocytopenia. If the latter patients, however, show a rash, the prognosis is poor. From 1985 to 1987, two types of LGL lymphocytosis, of which one type had a rash and poor prognosis and another has had a good and mild prognosis, were treated at Nihon University Hospital. This report presents the case reports. Case 1 : In October, 1987, a 28-yr-old male complained of low-grade fever. His leukocyte count was found to be 12.9 x 109/1, with lymphocytes occupying 57% of the leukocytes and showing three forms: lymphoblastoid cells without granulars, amounting to 9.5%; lymphoblastoid cells with azurophilic granules in the cytoplasma (LGL), amounting to 37.5%; and mature lymphocytoid cells, amounting to 10%. Bone marrow aspirates revealed normal cellularity with a mild infiltration of lymphoblastoid cells, with or without granules, amounting to 30%, and mature lymphocytoid cells amounting to 4.9%. An analysis of his PMNC showed the following phenotypes: CD2+, 3-, 4-, 5-, 8-, lo-, 11-, 16-, 19-, 20-, Leu 7-, NKH-1 +, and IgG-FcR-. His PMNC showed low cytotoxicity to K562 cells, percent cytotoxicity was 1 .O (E/T; 20:l). A chromosome analysis of 30/31 cells revealed 46XY, and 1/31 cells, 45-X, -Y, -16,6q +, + 2M. His LGL which, on October 22, had been measured as 33.5 x 109/1, had decreased on November 6 to 16.0 x 109/1, and the lymphoblastoid cells without granules increased from 2.4 x 109/1 to 34.8 x 109/l. Therefore, the patient was diagnosed as having acute natural killer cell leukemia and a combination chemotherapy using L-asparaginase, vincristine, and prednisolone was immediately started on November 6. However, nongranular lymphoblastoid cells increased daily and, finally, severe neutropenia occurred. The patient died of sepsis on December 28, 1987. Case 2: In May, 1985, a 51-yr-old male, complaining of numbness about both elbows, was thought to have leukocytosis (1). His peripheral leukocyte count was 12.4 x 109/1, and LGL occupied 79% of leukocytes. Neither anemia nor thrombopenia were noted. Hepatomegaly, splenomegaly, and lymphadenopathy were not noted. An analysis of PMNC showed the following phenotypes: CDl-, 2+, 3+ , 4-, 5 + , 8 + , lo-, 11+, 16.. 19-, 20-, Leu7+, NKH-I-, and IgG-FcR+. Cytotoxicity to K562 of PMNC was 4.1. Chromsosome analysis revealed 46XY. He was diagnosed as having LGL lymphocytosis, though he did not take therapy. For 3 yr and 9 months following this diagnosis, his leukocyte counts have ranged 12.0 x lo9 to 17.5 x 109/1, and LGL have continued to occupy 76% to 90% of the leukocytes. Case 3: In December, 1975, tests of a 71-yr-old female, complaining of easy fatigability, indicated mild hypertension and leukocytosis (2). Her peripheral leukocyte count was 13.5 x 109/1 with LGL occupying 88%. Her spleen was palpable to 3 cm below the left costal margin, though hepatomegaly or lymphadenopathy were not noted. Her PMNC revealed the following phenotypes: CD1-, 2+, 4+, 5 + , 8-, lo-, 11-, 16-, 19-, 20-, leu7+, NKH-I-, and IgG-FcR-. Cytotoxicity to K562 cells of PMNC was 1.3. Chromosome analysis revealed 46XX. She was diagnosed as having LGL lymphocytosis. For 13 yr and 3 months following diagnosis, she has not taken therapy. Her leukocyte count has ranged between 12.0 x lo9 to 19.0 x 109/1 and LGL have occupied 80% to 90% of leukocytes. Colony assay: Colony assays were done by employing the plasma clot culture method (3). 10% conditioned medium from the GCT cell line for the CFU-g assay and 1 unit/ml of human erythropoietin for the CFU-e assay were used. The influence of the PMNC of these patients was shown by the addition of 2 x 1 6 PMNC in colony assays of 5 x lo4 BMNC from these patients or from healthy donors. When BMNC were cultured with PMNC, the percentage of colony formation was calculated as equaling 100 x (number of colonies in the PMNC added culture number of spontaneous colonies) / (number of colonies in the culture of BMNC alone number of spontaneous colonies). The PMNC of Case 1, remarkably, inhibited the colony formation of autologous allogeneic CFU-g, and autologous CFU-e, p < 0.01. On the other hand, the PMNC of Cases 2 and 3 did not inhibit the colony formation of autologous and allogeneic CFU-g, and PMNC of case 2 did not inhibit the colony formation of CFU-e (Table 1). The influences of the PMNC from