Masako Katoh

Development of interstitial pneumonitis during treatment with granulocyte colony-stimulating factor.

Sir, Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor, widely used for the treatment of cytotoxic chemotherapy-induced neutropenia. We report two patients with malignant lymphoma who developed interstitial pneumonitis during or shortly after treatment with G-CSF. Recombinant human GCSF produced by Escherichia coli (Kirin Brewery Co. Ltd., Tokyo) was used in both patients. Patient 1 was a 66-year-old woman with non-Hodgkins lymphoma (diffuse large-cell type, stage liB). She was successfully treated with COPBLAM. After the second course of chemotherapy, her neutrophil count fell to 0.5 x 109/1. She received subcutaneous injections of G-CSF (1.5/zg/kg) for 4 days, and the neutrophil count recovered to 8 x 109/1. Nine days after the cessation of G-CSF treatment, the patient complained of serious dyspnea without fever. The neutrophil count was 5x109/1. Chest examination revealed bilateral fine crackles, and chest X-ray film showed reticular interstitial infiltrates. The pulmonary function tests revealed decreased PaO2 (29.3 torr) and decreased diffusion capacity (AaDO2 261 torr). Before the chemotherapy PaO2 had been 76 torr. The patient was diagnosed as having interstitial pneumonitis. In spite of intensive treatment with steroids, antibiotics, and mechanical ventilation for a month, she died of multiple organ failure. The total dose of bleomycin administered was 20 mg. Patient 2 is a 62-year-old woman with non-Hodgkins lymphoma (diffuse mixed-cell type, stage IVA, with skin infiltration). She was successfully treated

Neutrophil kinetics shortly after initial administration of recombinant human granulocyte colony-stimulating factor. Neutrophil alkaline phosphatase activity as an endogenous marker

Abstract: Recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) was administered (1.5 pg/kg body weight) subcutaneously once daily for 5 to 9 days to 5 patients with malignant lymphoma. In all patients, initial administration of rhG‐CSF induced a rapid fall in the neutrophil count within 30 minutes, followed by a recovery and an increase in the neutrophil count within 150 min. A rapid fall in the neutrophil count was accompanied by increased expression of neutrophil C3bi‐receptors, and neutrophils left in the circulation had lower activity of neutrophil alkaline phosphatase (NAP) and phagocytosis. A decrease in the NAP scores observed at 30 min reflected a preferential decrease of neutrophils with high NAP activity. A recovery and an increase in the neutrophil count were accompanied by a further decrease of NAP scores, which was caused by a preferential increase of neutrophils with lower NAP activity. The NAP scores of mature neutrophils from peripheral blood were not affected by in vitro treatment of cells with rhG‐CSF for up to 150 min at 37 °C. These findings and the previous observations that neutrophils in the circulating and marginal pools have high NAP activity and neutrophils in the bone marrow pool have low NAP activity taken together suggest that, following initial administration of rhG‐CSF, functionally active neutrophils leave the bloodstream preferentially, which is primarily followed by an influx of neutrophils from the bone marrow, but not by demargination of sequestered neutrophils.

Therapeutic effectiveness of ranimustine chemotherapy for elderly essential thrombocythemia

Background:  We studied the clinical effectiveness of ranimustine (MCNU) chemotherapy for essential thrombocythemia (ET).

Prognostic factors in elderly multiple myeloma patients aged 65 years or older : Comparison with nonelderly patients with multiple myeloma

Background:  Although age is a prognostic factor in multiple myeloma (MM), the prognostic factors in elderly MM patients may be different to those in nonelderly MM patients due to the patients age. The difference in the significance of prognostic factors between elderly MM patients and the nonelderly MM patients was studied.

Neutrophil functions in granulocyte transfusions mobilized by granulocyte colony-stimulating factor(G-CSF): Chemotaxis of neutrophils unchanged in healthy donors after the administration of G-CSF.

We attempted to investigate whether chemotaxis of neutrophils from healthy donors could be enhanced by G-CSF therapy. Two donors for granulocyte transfusions received intravenous administration of 2μg/kg G-CSF 16 hours before leukapheresis. Phagocytic activity of neutrophils from healthy donors after administration of G-CSF increased compared to those taken before G-CSF administration.In contrast, random mobility and chemotaxis toward Zymosan-activated serum and filtrate of E. coli were unchanged. After G-CSF administration, neutrophils collected by leukapheresis showed augumented chemotaxis and random mobility as compared with those collected by venipuncture. However, leukapheresis procedure had no effect on phagocytosis. Neutrophil function was not affected by irradiation. Concerning the discrepancy between chemotaxis and phagocytosis, an increased neutrophil adhesion may result in depressive chemotaxis and enhanced phagocytosis.And the fact that random mobility and chemotaxis of neutrophils enhanced after leukapheresis suggests that during the continuous flow centrifugation process, secondary cytokines may be released into circulation in response to G-CSF, which leads to the enhancement in neutrophil migration.

Disturbance of neutrophil functions by air pollution: Impairment of chemotaxis and phagocytosis of neutrophils from the diesel engine exhaust inhaled rats.

We attempted to investigate the effect of air pollution on functions of neutrophils collected from Fisher rats exposed to diesel engine exhaust. Rats were exposed either to a high concentration of diesel exhaust (H-group) or to the diesel exhaust from which particles deprived through filters (non-dust; ND-group) for six months. The concentration of NO2 gas and diesel exhaust particles was 2.6 ppm and 7.8 mg/m3 in H-group, and 2.1 ppm and 0.02 mg/m3 in ND-group, respectively. Phagocytic activity of the neutrophils from H-group was depressed. In addition, phagocytic activity of the neutrophils was further depressed in the ND-group. Neutrophil chemotaxis under agarose toward FMLP was decreased in either H-group or in ND-group, as compared with that of the control group.These findings suggest that the inhalation of NO2 may impair the peripheral blood neutrophil functions such as phagocytosis and chemotaxis. The preservation of the neutrophil phagocytic activity in H-group as compared with ND-group seems to be partly due to the modulation of the stimulated alveolar macrophage function by diesel particles ingestion, which may finally potentiate the neutrophil function. And the toxic gas elements of the inhaled exhaust may be easily absorbed into blood by reaching the higher concentration of gas to pulmonary alveolar regions, which leads to the deterioration of neutrophil phagocytic activity in ND-group.