Tatsuo Shirai

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.