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)

Of 320 patients receiving a marrow transplant at the Hospital de Sant Pau between 1986 and 1992, 12% developed viridans streptococcal bacteremia during severe neutropenia. Five of these patients (13%) developed a rapidly progressive fatal shock syndrome characterized by bilateral pulmonary infiltrates, acute respiratory failure (ARDS) and septic shock early in the transplantation course (6 or 7 days posttransplantation). All patients were transplanted for acute leukemia in remission, and 2 received an allogeneic and 3 an autologous transplant. Four of these subjects were younger than 15 years of age and all had received cyclophosphamide and total body irradiation as conditioning regimen for marrow transplantation. All 5 patients died, and postmortem examinations revealed diffuse pulmonary lesions characteristic of the ARDS. These observations contribute to defining the clinical and pathologic characteristics of this serious complication of intensive anticancer treatment.
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PMID:Viridans streptococcal shock syndrome during bone marrow transplantation. 748 15

Granulocyte colony-stimulating factor (G-CSF) shortens the duration of chemotherapy-induced granulocytopenia in acute leukemia. G-CSF is administered by 30-min intravenous infusion at a dose of 200 micrograms/m2/day or 5 micrograms/kg/day in most studies. In this study, the efficacy of a reduced dose (33 micrograms/m2/day) of continuous subcutaneous infusion of G-CSF was compared with the effects achieved by 30-min intravenous infusion of the standard dose (200 micrograms/m2/day) in neutropenia after identical chemotherapy in seven patients with acute myelogenous leukemia who were in remission. The duration of granulocytopenia (< 0.5 x 10(9)/l), thrombocytopenia (< 50 x 10(9)/l); G-CSF administration and fever (> 38 degrees C) were 10.1 +/- 5.0 days, 16.5 +/- 9.3 days, 16.6 +/- 7.4 days and 3.1 +/- 5.4 days for 33 micrograms/m2/day continuous subcutaneous infusion, and 10.7 +/- 6.8 days, 16.7 +/- 9.9 days, 16.1 +/- 7.6 days and 2.0 +/- 2.5 days for 30-min intravenous infusion of the standard dose of G-CSF. In each parameter studied, there was no statistical difference between the two methods of G-CSF administration by paired t-test. The costs for G-CSF could be substantially reduced. In most patients, plasma G-CSF concentration rose to the highest level of 1.8-3.7 ng/ml 48-72 h after starting 33 micrograms/m2/day continuous subcutaneous infusion, and gradually decreased as the peripheral granulocyte count recovered, suggesting binding of G-CSF molecules to the specific receptors on the cells of granulocytic lineage.
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PMID:Low-dose continuous subcutaneous infusion of granulocyte colony-stimulating factor for chemotherapy-induced neutropenia in acute myelogenous leukemia and its pharmacokinetics. 752 87

The granulocyte colony-stimulating factor (G-CSF) has been shown to accelerate recovery from severe neutropenia and to decrease the incidence of documented infections after intensive chemotherapy in cancer patients. However, the routine prophylactic use of G-CSF is expensive. This study was conducted to determine the role of G-CSF as adjunct therapy for septicemia following neutropenia caused by chemotherapy in children with acute leukemia. Fifty consecutive episodes of septicemia were studied involving 34 episodes of Gram-negative, 7 episodes of Gram-positive, 5 episodes of polymicrobial bacterial septicemia, one episode of fungemia, and 3 episodes of disseminated fungal infection. In the first 25 episodes, G-CSF was not used (group A). For the next 16 episodes, G-CSF 200 micrograms per square meter per day subcutaneously was given immediately after the septicemia was documented until the absolute neutrophil count was maintained at more than 1,500 per cubic millimeter (group B). Thereafter, G-CSF at the same dose as that of group B was prophylactically used in all the children who received high-dose cytosine arabinoside-containing regimens. Nine episodes of septicemia occurred (group C). The incidences of mortality per episode of septicemia in groups A, B, and C were 12.0% (3/25), 12.5% (2/16) and 0% (0/9), respectively. Statistically, there was no difference between the three groups overall and in pair-wise comparisons (all P > 0.5). The durations of G-CSF administration in group B ranged from 6 to 26 days with a median of 12 days and the durations of G-CSF administration in group C ranged from 10 to 23 days with a median of 19 days. With or without G-CSF, there may be no significant difference in the mortality of septicemia following neutropenia caused by chemotherapy in children with acute leukemia.
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PMID:Role of granulocyte colony-stimulating factor as adjunct therapy for septicemia in children with acute leukemia. 753 94

During a 22-year period, 13 patients with hematologic diseases developed bacteremia caused by the Bacteroides fragilis group, with a frequency which remained almost unchanged. Nine patients (69%) had polymicrobial infections. Acute leukemia was the most common underlying disease. The lower intestinal tract (necrotizing enterocolitis and anorectal abscesses) was the most common source of infection. Prior antibiotic therapy was the most frequent host condition before bacteremia, followed by cancer chemotherapy, neutropenia, thrombocytopenia and hypoproteinemia. Septic shock occurred only in seven patients with polymicrobial infections. Six patients, including five with shock, died within a week of onset, while the other seven survived for at least three weeks. Despite its clinical similarity to aerobic gram-negative infection, bacteremia due to the B. fragilis group may well, therefore, be suspected particularly when neutropenic patients who present with lower intestinal symptomatology develop a persistent fever unresponsive to the initial empiric antibiotic therapy.
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PMID:Bacteremia caused by the Bacteroides fragilis group in patients with hematologic diseases. 759 53

This study evaluates the sensitivity and positive predictive value of some of the morphological flags supplied by the Technicon H-1 haematological analyser to detect circulating blasts. A total of 1,269 venous blood samples from 91 paediatric patients diagnosed of acute leukemia were analysed in the Technicon H-1. A conventional microscopic manual method was used for reference. The prevalence was 17.7% for the presence of blasts. The results showed that all samples with more than 5% blasts were detected by some WBC morphological flag: only 5 samples (2.2%) with less than 5% blasts showed no morphological flag. In most cases (86%), the flags observed were either the 'Atyp' flag or the 'Blast' flag or both simultaneously. The positive predictive value obtained by the 'Blast' flag for the true presence of blasts was 66.8%, and for the 'Atyp' flag 34.9%; it was 75.8% when both flags were present simultaneously. False positives were associated with postchemotherapy monocytosis or severe neutropenia.
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PMID:Utility of the Technicon H-1 flags in the detection of peripheral blood blast cells of paediatric acute leukaemia patients. 772 55

Neutropenia is the major factor predisposing to sepsis in cancer patients, and its duration is important for survival. We administered leukocyte transfusions (LT) to 10 children suffering from documented life-threatening infections during profound, prolonged neutropenia. Nine had acute leukemia, and one had aplastic anemia; three were bone marrow transplant recipients. These 10 were the only patients in our unit who received LT during the past 7 years. The median leukocyte dose was 0.6 x 10(9)/kg in total. Instead of leukapheresis products, we used pooled buffy coats from random donors, with a high relative content of lymphocytes and especially T lymphocytes. The leukocyte concentrates were irradiated with 15 Gy. In all 10 patients, we observed prompt and sustained myeloid marrow recovery following LT. Such an effect of LT has never been described before. We hypothesize that in the internal milieu of these aplastic patients the transfused leukocytes were stimulated to secrete cytokines, the result being a cascade-like phenomenon and stimulation and proliferation of the patient's own bone marrow cells. The bone marrow-stimulating effect of LT merits further study.
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PMID:Reemphasis on leukocyte transfusions: induction of myeloid marrow recovery in critically ill neutropenic children with cancer. 776 27

Acute promyelocytic leukemia (APL) provides a model to examine the sequential use of selective oncogene product-targeted and lineage-targeted agents. All-trans retinoic acid (RA) has been shown to produce brief remissions by a novel differentiating mechanism in most patients with APL. M195, a mouse monoclonal antibody (moAb) reactive with the cell-surface antigen CD33, can target myeloid leukemia cells in patients and reduce large leukemic burdens when labeled with 131I. We studied whether 131I-M195 could safely reduce minimal residual disease and prolong remission and survival durations in patients with relapsed APL after they had attained remission with all-trans RA. Seven patients with relapsed APL in second remission were treated with either 70 (n = 2) or 50 (n = 5) mCi/m2 of 131I-M195. As a measure of minimal residual disease, we serially monitored PML/RAR-alpha mRNA by a reverse transcription polymerase chain reaction (RT-PCR) assay. There was no immediate toxicity. Late toxicity was limited to myelosuppression, but no episodes of febrile neutropenia were seen. Six patients had detectable PML/RAR-alpha mRNA after all-trans RA therapy; two had single negative RT-PCR determinations following 131I-M195. Median disease-free survival of the seven patients was 8 months (range 3-14.5). Four patients with median follow-up of 24 months remain alive, and median overall survival exceeds 21+ months (range 5.5-33+). This regimen based on targeted therapy compares favorably to other approaches for the treatment of relapsed APL, including that used in the immediately preceding trial in which patients were induced into remission and maintained with all-trans RA, as well as other chemotherapy-based regimens. These data support further study of moAb-based therapy for minimal residual disease in acute leukemia.
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PMID:Sequential targeted therapy for relapsed acute promyelocytic leukemia with all-trans retinoic acid and anti-CD33 monoclonal antibody M195. 786 59

Two patients with acute leukemia developed Escherichia coli bacteremia while receiving oral ofloxacin for antibacterial prophylaxis during profound neutropenia. The isolates were resistant to ofloxacin (MIC 25 and 12.5 micrograms/ml respectively), other fluoroquinolones and several unrelated agents. Whole cell drug accumulation studies with four different fluoroquinolones suggested major differences between drugs but only minor alterations in individual drug permeability in the two resistant isolates compared with a susceptible control strain. In a supercoiling assay using the purified DNA gyrase and plasmid pBR322, high concentrations (> or = 250 micrograms/ml) of both ofloxacin and ciprofloxacin were needed for visible inhibition of enzyme activity suggesting mutations in the DNA gyrase gene as the significant mechanism of resistance in both strains.
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PMID:Bacteremia due to fluoroquinolone-resistant Escherichia coli in two immunocompromised patients. 801 90

Etoposide has been used in the treatment of a wide variety of neoplasms, including small-cell lung cancer, Kaposi's sarcoma, testicular cancer, acute leukemia, and lymphoma. Its current therapeutic use is limited by myelosuppression, particularly neutropenia. Pharmacodynamic studies of etoposide show that this toxicity can be modeled using a modified Hill equation and that the dose intensity of etoposide can be successfully increased by adaptive control using this model. Significant influences on the degree of myelosuppression include the pretreatment leukocyte count, the performance status, the extent of prior erythrocyte transfusions, and the serum albumin level. In the past 7 years, interest has developed in a distinct subset of acute nonlymphocytic leukemia that is associated with prior exposure to etoposide. This syndrome has been described in several studies and is characterized by the lack of a preleukemic phase, M4 or M5 morphology, and distinct translocations involving the chromosome 11q23 region. In addition, secondary acute lymphocytic leukemias (involving 11q23) have also been associated with prior epipodophyllotoxin exposure.
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PMID:Pharmacodynamics and long-term toxicity of etoposide. 807 30

High-dose chemotherapy regimens can cure a number of otherwise incurable diseases, such as Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, acute leukemia (in remission), and breast cancer. Trials of high-dose chemotherapy have generally used autologous bone marrow transplant or peripheral blood stem cell support to ensure hematologic recovery after intensive chemotherapy and/or radiation. This report describes an approach in which high-dose carboplatin chemotherapy was followed initially by granulocyte-macrophage colony-stimulating factor (GM-CSF; Escherichia coli. Sandoz-Schering, East Hanover and Kenilworth, NJ) and in subsequent patients, by both GM-CSF and repeated cycles of peripheral blood progenitor cell (PBPC) collection and administration. The addition of PBPC to this regimen led to significant reductions in the duration of neutropenia and thrombocytopenia, the requirement for erythrocyte and platelet transfusions, the length of hospital stay, and the use of intravenous antibiotics in this group relative to those patients who received GM-CSF alone. In addition, laboratory studies are presented that show a direct correlation between the number of progenitor cells reinfused and the duration of neutropenia and thrombocytopenia. The report also reviews data indicating that circulating progenitor cells are depleted by this approach. This suggests that the number of progenitor cells available for mobilization is finite. Finally, the magnitude of these effects, and their implications for future trials with repetitive cycles of dose-intensive therapy, are discussed.
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PMID:High-dose carboplatin chemotherapy with GM-CSF and peripheral blood progenitor cell support: a model for delivering repeated cycles of dose-intensive therapy. 810 54


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