Summary
Secondary infections related to neutropenia and functional defects of phagocytes are common outcomes in cancer-treated patients. Hematopoietic colony-stimulating factors (CSFs) have been introduced into clinical practice as additional adjuvant measures that may reduce the incidence of infectious complications in patients with cancer and neutropenia.
The aim of this study was to determine the role of granulocyte/macrophage (GM)-CSF and granulocyte (G)-CSF in enhancing in vivo human neutrophil function. A luminol-dependent chemiluminescence assay was developed to evaluate whether neutropenia has to do with the ability of neutrophils to perform repair function. A single dose of 5 µg G-CSF kg(-1) day(-1) [recombinant human (RHU) G-CSF; filgrastim] or 250 µg GM-CSF m(-2) day(-1) (rHu GM-CSF; molgramostim) administered subcutaneously once daily to 12 metastatic cancer patients being treated with various cytotoxic regimens Was. All injections of CSF were given after the onset of neutropenia and continued until the occurrence of a complete neutrophil recovery. rHu GM-CSF and rHu G-CSF administered once a day at 250 µg m(-2) day (-1) and 5 µg kg(-1) day (-1),
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Materials and methods
study population. Patients were included if they presented with (1) a clinical and radiological picture consistent with active pulmonary TB, and vigorously according to the acid-fast-bacilli (AFB) method in two consecutive sputum smears. were positive smears (3 plus); (2) were between 18 and 50 years of age; (3) had no history of previous TB treatment; and (4) had leukocyte counts below 25,000/mm at 3 admission. Patients were excluded if they (1) presented with any serious concomitant diseases, such as severe pulmonary dysfunction, renal, cardiac, hematological or liver disease; (2) had severe dermatological lesions above grade 3 on the WHO score system; (3) were pregnant or lactating women; (4) had a history of alcohol abuse, had diabetes mellitus, had mental disorders, were HIV or HTLV-I/II positive; (5) were receiving immunosuppressive treatment; or (6) could not provide informed consent or could not be followed after a period of hospitalization. Administration of previous or concomitant drugs such as antimycobacterial drugs was not permitted during the study period.
All patients gave written informed consent before entering the study.
Randomization and study treatment. After diagnosis of tuberculosis, patients meeting all admission criteria were hospitalized for at least the first two weeks to allow a better clinical assessment of tolerability. Patients were randomized to take either rhu-GM-CSF 125 µg/m2/dose) twice a week for four weeks, or a placebo, both supplied by Immunex Corporation. Neither the doctor nor the patient knew what medicine they were taking. In addition to challenge treatment, all patients weighing more than 45 kg to take rifampin (600 mg/day) + isoniazid (400 mg/day) daily for six months and pyrazinamide (2000 mg/day) for the initial two months was scheduled. Patients weighing less than 45 kg were prescribed 450 mg/day rifampin + 300 mg/day isoniazid for six months and 1500 mg/day pyrazinamide for the initial two months.
Colony-stimulating factors (CSFs) are secreted glycoproteins that bind to receptor proteins on the surfaces of hemopoietic stem cells, thereby activating intracellular signaling pathways that allow cells to grow and develop into a specific type of blood cell (usually white blood cells). can cause the difference. .
Description: Recombinant human GM-CSF produced in E.coli is a single, non-glycosylated, polypeptide chain containing 127 amino acids, two pairs of disulfide bonds and having a molecular mass of approximately 14.5kD.