MORPHOLOGIC CHANGES OF NEUTROPHILS IN MYELODYSPLASTIC SYNDROME TREATED WITH RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR

Two cases of myelodysplastic syndrome (MDS) were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF). In both cases, an increase of peripheral neutrophil counts was noted with a peak within 12 hr after the rhG-CSF administration. Neutrophils with ring shaped or hypersegmented nuclei were noted in the peripheral blood during the treatment, and they disappeared promptly after discontinuation of the therapy. The results indicate that the rhG-CSF might have mobilizing and differentiating effects on neutrophils derived from the MDS clone.     

Binding Properties and Proliferative Effects of Human Recombinant Granulocyte-Macrophage Colony-stimulating Factor in Primary Leukemia and Lymphoma

Binding of radiolabeled human granulocyte-macrophage colony-stimulating factor (GM-CSF) was studied with blast cells front eight patients with acute myeloblastic leukemia (AML), and neoplastic lymphoid cells from one patient with acute lymphoblastic leukemia (ALL), two patients with chronic lymphocytic leukemia (CLL) and one patient with undiagnosed B cell neoplasia. In all AML cases studied, Scatchard graphs of the direct binding data were curvilinear, and were best fitted by curves derived from a two-binding-site model; one site with high affinity ( K d₁= 12–71 p M ; 174–602 sites/cell) and the other with low affinity ( K d₂= 0.5–2,7 n M ; 1137–6020 sites/cell). A cross-linking study on blast cells from one AML patient demonstrated specific bands which were similar to those reported for peripheral blood neutrophils. Furthermore, blast colony assays for the same preparations showed remarkable proliferative response to GM-CSF in the concentration range from 0.3 n M to 7.0 n M (ED₅₀ >0.7 n M ). This concentration range is approximately one order of magnitude higher than that which is effective for colony formation from normal bone marrow progenitors (ED₅₀= 0.l n M ). No significant correlation could be observed between the responsiveness of blast progenitors to GM-CSF, and the numbers or affinities of GM-CSF binding sites demonstrated on blast cells. In studies with neoplastic lymphoid cells from four patients, ¹²⁵I-GM-CSF also specifically bound in two cases, while response to GM-CSF was not observed in these cases. These results indicate that the expression of GM-CSF receptor is not restricted to the GM-CSF-responsive AML blast cells, but can be observed in other AML blast cells and even in neoplastic lymphoid cells.     

An early phase II clinical study of YM 294 (rhlL-11) in patients with solid tumors and malignant lymphoma

An early phase II study was conducted to examine the efficacy and safety of YM 294 on chemotherapy-induced thrombocytopenia in patients with solid tumors and malignant lymphoma. The response rates which were judged as having good or excellent efficacy by the investigators were 66.7% in all groups with 25 microg/kg or more, and the increase in nadir platelet counts and decrease in platelet transfusions were observed. Adverse reactions were fever, edema, abnormal electrocardiogram and weight gain. All adverse reactions as well as abnormal changes in laboratory values for which the casual relationship with the study drug could not be excluded were resolved and proved to be not serious. The results of this study suggest the efficacy of YM 294 at 25 microg/kg or more for chemotherapy-induced thrombocytopenia in patients with solid tumors and malignant lymphoma. It was considered that a study should be performed to assess the efficacy and safety of YM 294 using a dose of 25 microg/kg or more in the future.     

Low C3B receptor reactivity on erythrocytes from patients with systemic lupus erythematosus detected by immune adherence hemagglutination and radioimmunoassays with monoclonal antibody

C3b receptor (CR1) on erythrocytes from 23 patients with systemic lupus erythematosus (SLE) and 124 normal controls was determined by immune adherence hemagglutination (IAHA) and radioimmunoassay. The binding of radiolabeled monoclonal anti-CR1 to erythrocytes and their lysate was distributed continuously in a wide range. The majority of SLE patients showed low binding by both assays. CR1 sites on erythrocytes were determined also by Scatchard plot analysis and standardized by the number of similarly determined lectin-binding sites that served as a measure of erythrocyte surface. The numbers of standardized CR1 sites were classified as high, intermediate, and low. Thirty-six percent of control subjects had high numbers of CR1 sites, 53% had intermediate numbers, and 11% had low numbers. Of SLE patients, the numbers of CR1 sites were high in 0%, medium in 52%, and low in 48%. Negative IAHA was found in 10 controls (8%), all of whom had low numbers of standardized CR1 sites. Among 13 SLE patients with negative IAHA, 11 had low numbers of CR1 sites and the remaining 2 had low intermediate numbers. IAHA, therefore, was particularly efficient in detecting the low numbers of CR1 sites in SLE, which would impair the disposal of circulating immune complexes and accelerate the development of tissue injuries.