Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0027947 (neutropenia)
17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of various regimens of cyclophosphamide administration on guinea pig peripheral blood leukocytes were studied. Cyclophosphamide-induced immunosuppression was assessed by the effect of drug administration on the proportions and absolute numbers of leukocyte populations, and by the effect on functional capabilities of unfractionated and adherent cell-depleted mononuclear cell suspensions as measured by the PHA-induced cellular cytotoxicity and antibody-dependent cellular cytotoxicity assays against chicken erythrocyte targets. Intraperitoneal administration of five daily doses of cyclophosphamide (5 mg/kg) caused a modest absolute leukopenia but no change in cytotoxic effector function of the mononuclear cells remaining in the circulation. As the dosage of cyclophosphamide was increased to 20 mg/kg/day to produce a pronounced leukopenia, a profound neutropenia (less than 300 polymorphonuclear leukocytes/mm3) together with a marked decrease in mononuclear cell effector function was noted. A single i.p. injection of cyclophosphamide (100 mg/kg), which produced identical degrees of leukopenia of each leukocyte class as did daily administration of cyclophosphamide (20 mg/kg/day), caused no change in mononuclear cell effector function when compared to saline controls. Complement receptor-bearing and Fc-receptor bearing mononuclear cells were decreased to the same degree by both regimens of cyclophosphamide administration. Removal of adherent cells from mononuclear cell suspensions by column purification resulted in a marked decrease in cytotoxic effector function at low effector to target ratios. At higher effector to target ratios there was no difference in cytotoxic effector function between unfractionated and column-purified cells. In contrast, the functional defect in mononuclear cell suspensions from animals that received five daily doses of cyclophosphamide (20 mg/kg) could not be compensated for at higher effector to target ratios, indicating that this functional defect was not an artifact of relative depletion of monocytes by cyclophosphamide, but was due to an actual suppression of the effector functional capabilities of the killer cells. This study indicates that, dependent on the particular regimen of drug administration, the quantitative depletion of mononuclear cell populations by cyclophosphamide administration can be clearly distinguished from the qualitative effect on certain functional capabilities of surviving cells.
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PMID:Divergent effects of cyclophosphamide administration on mononuclear killer cells: quantitative depletion of cell numbers versus qualitative suppression of functional capabilities. 93 31

The characteristics of cyclophosphamide-induced suppression of established ccll mediated immunity were studied in guinea pigs previously senstized to tuberculin. Cyclophosphamide treatment for 5 days produced a dose-dependent peripheral lymphoctopenia and disproportionatley greater neutrophenia which was particularly striking at high doses of 20 mg/kg per day(approximaetly 200 mg/kg-2 per day). Lymphoctes remianing in the circulation of cyclophosphamide treeated aniamls showed a doses-dependent reduction to both in vitro proliferactive and macrophage migration inhibitory factor responses to tuberculin compared to lymphocte responses of controls. Proliferative responses to phytohemaggultinin and concanavalin a were not significatly suppressed. Additional studies showed that cyclophosphamide suppressed the porliferactive and migration inhibitroy factor responses to tuberculin of lymph node and splenic as well as cirulating lymphocte populations. These studies showed that relatively short-term cyclophospamide administration produced immunosuppresion by quantitative as well as qualitative changes in lymphocyte populations. Significant suppresion of lymphocte function, howerver, was achived only with doses of cyclophoshamide which also produced a severe neutropenia.
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PMID:Cyclophosphamide suppression of established cell-mediated immunity. Quantitative vs. qualitative changes in lymphocyte populations. 109 12

We have treated sixty-two patients (21 with limited disease, 41 with extensive disease), on an outpatient-basis schedule of six drugs administered weekly for twelve weeks. Cyclophosphamide, 400 mg/m2, adriamycin, 20 mg/m2 and vincristine, 2 mg, full dose, were administered during weeks 1, 5 and 9; cisplatin, 50 mg/m2 and etoposide, 100 mg/m2 during weeks 2, 6 and 10; adriamycin and vincristine at the same doses during weeks 3, 7 and 11; methotrexate 30 mg/m2, during weeks 4, 8 and 12. After the first 28 patients vincristine was replaced by teniposide (VM-26) due to neurotoxicity. The overall response rate was 64.5% (complete remission 13 p., partial remission 27 p.). Toxicity grade 3-4, mainly nausea and vomiting or neutropenia, was recorded in 17 patients. Alopecia grade 1-2 was universal. One toxic death occurred from sepsis. The overall survival was 8 months (range 1-40), (95% CL: 53-77%); 8 months in limited disease (range 1-40), and 7 months in extensive disease (range 1-23). Time to treatment failure was 6 months (7 limited disease, 5 extensive disease). In conclusion, the results of this alternating schedule are poorer than those attained with standard, high-dose treatments, mainly in limited disease, but could be a less toxic option for patients with extensive disease.
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PMID:Alternating chemotherapy for small-cell lung cancer. A twelve-week schedule of six drugs. 131 40

Neutropenia is a major cause of chemotherapy-induced morbidity. This study examines the effect of ImuVert on the course of neutropenia from Cytoxan and Adriamycin. In adult rats treated with either Cytoxan or Adriamycin and ImuVert, the absolute neutrophil count remained above 7,000 and 2,000, respectively, for the duration of ImuVert therapy. In contrast, in the control Cytoxan group the absolute neutrophil count reached 300/mm3 on day 5 and remained below 1,000 from day 4 through day 7. In the Adriamycin control group, the nadir absolute neutrophil count reached 600/mm3 on day 7 and remained below 100 from day 6 through day 8. C3H/EJ mice (endotoxin-hyporesponsive) treated with Cytoxan developed an absolute neutrophil count below 1,000 from day 4 through day 7. In contrast, in the group concomitantly treated with ImuVert, the nadir absolute neutrophil count remained below 1,000 only on days 4 and 5. The authors conclude that stimulation of endogenous cytokine production by ImuVert may provide a potentially useful approach to bone marrow rescue from chemotherapy.
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PMID:Protection from chemotherapy-induced neutropenia by ImuVert. 153 14

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).
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PMID:Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B. 163 44

We have evaluated the effect of Interleukin-2 [IL-2] after Cyclophosphamide (C) chemotherapy in 41 patients with metastatic cancer. IL-2 was given as a continuous infusion priming cycle 36 hours after C at 1 gm/m2 intravenously. In 39 evaluable patients, there were no complete remissions [CR], 2 partial remissions [PR], and 1 had a minor response [MR]. Stable disease for 30 days was seen in 16 patients whereas 20 progressed. The durations of partial and minor responses were brief, ranging from 1-6 months. Grade 3-4 neutropenia was seen in 41%. This was more severe than seen with IL-2 alone or IL-2 combined with lower doses of C. The marrow suppression was due to the chemotherapy. This combination of IL-2 and C appears to be reasonably well tolerated by patients, but toxicity is greater and the response rate is no better than results achieved by IL-2 alone. Responses of 26 patients with renal cancer appear to be inferior to our historical data using IL-2/LAK cells without C. Immune monitoring demonstrated changes expected with C chemotherapy (i.e., a non-selective decline in immune function). C induced no further differences in IL-2 induced changes in immune function.
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PMID:Continuous infusion of interleukin-2 and cyclophosphamide as treatment of advanced cancers: a National Biotherapy Study Group Trial. 191 Jun 23

Cyclophosphamide (Cy), an alkylating agent widely used in chemotherapy of leukemia and cancer, causes a well-documented toxicity on hematopoietic and lymphoid cells. Neutropenia is thought to be the main factor involved in infectious complications following antimitotic chemotherapy. Little is known on the effects of these therapies on the mucosal associated lymphoid system which is one of the main barriers against environmental pathogenic agents. The present study examined the effects of a single administration of Cy (200 mg/kg) on murine T and B cell populations of Peyer's patches (PPs), IgA secretion in the proximal part of the small intestine, and plasma cells of the lamina propria. Cy induced in mice a transient decrease in the T and B cell populations of the PPs with a drastic fall of B cell counts and a profound decrease of intestinal IgA secretion due to a reduction of lamina propria plasma cells. This transient secretory IgA deficiency may contribute to the infectious complications following antimitotic chemotherapy.
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PMID:Transient secretory IgA deficiency in mice after cyclophosphamide treatment. 195 41

To assess how well chemotherapy is tolerated after solid organ transplantation, we reviewed our experience at the Children's Hospital of Pittsburgh with five patients aged 1 to 12 years. Four patients had a liver transplant, indications for which were hepatoblastoma in two patients, hepatic failure secondary to Wilms' tumor chemoradiotherapy in one patient, and familial intrahepatic cholestasis in one patient. A fifth patient received a cardiac transplant for unresectable angiosarcoma of the right atrium. After transplant, chemotherapy was given for the treatment of the primary malignancy in four of the patients. The patient with familial intrahepatic cholestasis received chemotherapy for secondary lymphoproliferative disease that had not responded to the cessation of immunosuppression. All patients other than this patient were on immunosuppression with prednisone (0.5 to 2 mg/kg daily) and cyclosporine (to maintain serum levels at 800 to 1000 ng/ml radioimmunoassay) throughout the duration of chemotherapy. Courses of chemotherapy included one or more of the following agents: Adriamycin (Adr, 20 mg/m2 daily, three patients), Cyclophosphamide (Ctx, 1 gm/m2, one patient), cisplatin (CDDP, 90 mg/m2, one patient), Vincristine (Vcr, greater than 0.75 to 1.5 mg/m2, three patients), Actinomycin D (Act-D, 7.5 micrograms/kg, one patient), Ifosfamide (I, 1800 mg/m2, one patient) and Etoposide (VP-16, 100 mg/m2, one patient). All patients received greater than or equal to 3 courses (range, 3 to 9; mean, 5) of chemotherapy every 3 to 4 weeks. Dose reductions were made because of neutropenia in three patients but none were greater than 50%. Severe rejection was seen in one patient who had, however, manifested evidence of rejection prior to his first postoperative course of chemotherapy. No nephro or cardiac toxicity was seen. This preliminary experience suggests that chemotherapy is well tolerated after solid organ transplantation.
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PMID:Cancer chemotherapy after solid organ transplantation. 220 97

Drugs possessing membrane stabilizing activity might act to diminish the augmented microvascular permeability resulting from acute lung injury. To test this rats were pretreated with quinidine, procainamide, or lidocaine and then given the lung injury-inducing agent thiourea. Vascular permeability, assessed as the extravascular accumulation of radiolabeled protein, was increased more than threefold by thiourea. This increase was diminished by 29, 34, and 43% after pretreatment with procainamide, quinidine, and lidocaine, respectively. Lidocaine also returned the thiourea-induced increase in lung wet weight-to-dry weight ratios to control levels. This protection was not likely due to hemodynamic effects of these agents, since no differences were noted in cardiac output between pretreated rats and those receiving thiourea alone and a small increase in mean pulmonary arterial pressure in the lidocaine-pretreatment group was the only difference noted. O2 metabolites have been implicated in the pathogenesis of thiourea-induced lung injury. None of these agents scavenged O2- or H2O2 directly, but quinidine and procainamide diminished in vitro neutrophil O2- and H2O2 production, and lidocaine inhibited neutrophil H2O2 production. However, neutropenia (PMN less than 100/ml) induced with either vinblastine or cyclophosphamide (Cytoxan) failed to prevent thiourea-induced increases in pulmonary vascular protein leak. In conclusion, procainamide, quinidine, and lidocaine diminished lung injury in rats after thiourea. Although these agents diminish PMN O2 metabolite production in vitro their salutary role in thiourea-induced lung injury appears to be through an unknown mechanism that is independent of their effects on neutrophil O2 metabolite-dependent toxicity.
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PMID:Antiarrhythmic agents diminish thiourea-induced pulmonary vascular protein leak in rats. 312 76

Experimental hypoplasia of femoral bone marrow in rats was induced by cyclophosphamide, injected i.p. at various clock hours (08.00, 12.00, 16.00, 20.00, 24.00, and 04.00). Cyclophosphamide-induced neutropenia persisted for six days and was followed by transitory granulocytosis with subsequent decrease in the cont of circulating mature granulocytes. The absolute counts of circulating segmented neutrophils changed in parallel with the absolute counts of segmented neutrophils in the bone marrow. The count of circulating neutrophils was not essentially influenced by the clock hour of cyclophosphamide injection. The toxic action of cyclophosphamide upon the bone marrow exhibited a circadian rhythmicity: the greatest decrease in the count of nucleated marrow cells was found in the morning, and the least, in the evening. The minimal compartment transit times of the development stages of bone-marrow neutrophils, and the daily granulocyte production in the rat were calculated.
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PMID:Leucokinetic study. Morphology of the bone marrow and blood after experimental induction of marrow hypoplasia by cyclophosphamide in laboratory rats. 616 52


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