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 characteristics of 554 febrile episodes in 126 patients with a hematological malignancy over a 6-year period (1985-90) were reviewed in order to study the current incidence and clinical significance of blood culture positivity. An infection was documented microbiologically in 28% and clinically in 30% of the episodes. Blood cultures were positive in 19% of the febrile episodes. The rate of blood culture positivity was unrelated to the type of hematological malignancy, to neutropenia and to the presence of infection foci. 21% (26/126) of the patients died of sepsis-related causes. Sepsis-related death occurred in 23% of the blood culture positive febrile episodes, with a median survival time of 2 days. Infection prophylaxis did not reduce either the rate of blood culture positivity or the rate of sepsis-related deaths. Thus, the small proportion of febrile episodes whose fever etiology could be established by blood culture represented 'the tip of the iceberg', i.e. rapidly lethal septic infections with a high mortality rate. This fatality could neither be predicted by a search for infection foci nor prevented by infection prophylaxis.
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PMID:Incidence and clinical significance of positive blood cultures in febrile episodes of patients with hematological malignancies. 819 Dec 44

Considering the beneficial effect of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), it has been speculated that ATRA might also be useful for treating other hematologic malignancies. To test this hypothesis, we performed a dose-escalating 3-month-trial of ATRA in 15 patients with primary or secondary myelodysplastic syndromes (MDS). Morphologic diagnoses were refractory anemia (RA) in 4, RA with ring sideroblasts (RARS) in 2, RA with excess blasts (RAEB) in 7, and RAEB in transformation (RAEB/T) in 2 cases. Patients included were required to have one or more of the following criteria: transfusion-dependent anemia, pronounced neutropenia (< or = 0.5 x 10(9)/L) or thrombocytopenia (< or = 20 x 10(9)/L), or increasing blast cells in the peripheral blood or bone marrow. Therapy was started at an ATRA dose of 30 mg/m2/d, administered orally as two doses of 15 mg/m2 every 12 hours. The retinoid dose was increased to 60 mg/m2/d after 4 weeks and to 90 mg/m2/d after 8 weeks. Among 14 patients assessable for response, none obtained a complete or partial remission. Three patients had a minor response, manifested by either reduction in transfusion requirements (2 patients) or increase in neutrophil and platelet counts (1 patient). During the study period, 5 patients progressed to more advanced stages of MDS or overt leukemia. Three patients with chromosomal abnormalities receiving ATRA for a period of 10 to 12 weeks retained their cytogenetic marker after completion of treatment. Side effects of ATRA primarily affected the skin and mucous membranes, with 13 of 15 patients having at least low-grade dermatologic toxicity. In 2 cases, treatment had to be prematurely stopped because of intolerable conjunctivitis or progressive neurologic symptoms. These data suggest that ATRA has little effect on MDS. The lack of response of MDS patients, as compared with those with APL, may be attributed to the absence of the t(15;17) translocation that seems to be a prerequisite for clinical efficacy of ATRA.
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PMID:All-trans retinoic acid in patients with myelodysplastic syndromes: results of a pilot study. 821 88

Ten patients with newly diagnosed haematological malignancy were given ofloxacin, 400 mg daily orally, for antibacterial prophylaxis during neutropenia. Before cytotoxic chemotherapy was given, and on three occasions between days 2-3, 5-7 and 8-10 afterwards, blood samples were taken before and 1, 2, 3, 4, 6 and 10 h after administration of ofloxacin. Serum ofloxacin concentrations were measured by HPLC. Mean (range) pharmacokinetic parameters before chemotherapy were: Cmax, 6.1 (2.7-9.1) mg/L; AUC0-2, 7.5 (1.9-11.6) mg.h/L. On days 2-3 post-chemotherapy the values were reduced to: Cmax, 5.0 (3.6-7.3) mg/L; AUC0-2, 5.8 (1.9-7.8) mg.h/L. On days 5-7 the values were: Cmax, 6.1 (4.0-10.4) mg/L; AUC0-2, 8.5 (0.8-16.8) mg.h/L, and by days 8-10 the values were: Cmax, 6.4 (3.3-12.5) mg/L; AUC0-2, 8.6 (0.8-23.1) mg.h/L. There was a statistically significant difference between Cmax pre- and Cmax two to three days post-chemotherapy (paired t-test, P = 0.05). These changes are similar to those previously reported with ciprofloxacin but less marked.
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PMID:Absorption of oral ofloxacin after cytotoxic chemotherapy for haematological malignancy. 822 2

Invasive fungal sinusitis is becoming increasingly common in patients undergoing BMT. This study was undertaken to evaluate the incidence, presenting symptoms, diagnosis procedures, treatment and outcome of invasive fungal sinusitis. The study population comprised 423 consecutive BMT patients at Hadassah University Hospital from January 1986 to August 1992. Eleven patients (2.6%) developed invasive fungal sinusitis, 8 had underlying hematologic malignancies and 3 severe aplastic anemia (SAA). Median interval between BMT and fungal sinusitis was 22.5 days (range 2-106 days). Eight of 11 patients had protracted neutropenia (median 8 days with median neutrophil count at the time of fungal sinusitis diagnosis of 0.25 x 10(9)/l). Four patients developed GVHD before fungal sinusitis was diagnosed. Presenting symptoms were fever (100%), orbital swelling (63%), facial pain (54%) and nasal congestion (36%). In 8 patients Aspergillus species were isolated (A. flavus in 7, A. quadrilineatus in 1); in 1 patient Candida albicans was isolated and in the other 2 fungal elements were detected histologically (Fusarium and Mucor, respectively). Six of the patients underwent surgical debridement at diagnosis. Three received granulocyte transfusions. All patients received systemic amphotericin B (7 conventional and 4 amphotericin B colloidal dispersion (ABCD)). Only 2 of the 11 patients responded completely to therapy with a follow-up of 15 months. It appears that invasive fungal sinusitis is a potentially fatal complication in immunocompromised patients post-BMT. Current treatment approaches are largely ineffective and new methods of management of this serious problem are needed.
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PMID:Invasive fungal sinusitis in patients undergoing bone marrow transplantation. 824 77

Bacteremia is one of the important complications of the treatment of hematological malignancy. In this report, we analyze bacteremias in 72 children with acute lymphoblastic leukemia who were admitted to our hospital from July 1, 1988 to October 31, 1991. Positive blood cultures were found in 26% (19/72) of the patients. There were 24 episodes of bacteremia; Gram-negative, Gram-positive and mixed bacteremia comprised 62.5% (15/24), 33.3% (8/24) and 4.2% (1/24), respectively. E. coli, klebsiella pneumoniae and Pseudomonas aeruginosa were the three most common pathogens. Eighty-three percent of the bacteremic episodes occurred during neutropenia (absolute neutrophil count below 500/mm3). Our data suggest that a Pseudomonas etiology, associated pneumonia, and shock accounted for a poor outcome. The over-all mortality for bacteremic events was 26.3% (5/19). Intensive supportive treatment and effective antibiotics are the most important factors in improving the outcome of bacteremia. The success in recent ALL treatment can be attributed in part to the improved outcome of bacteremia.
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PMID:Bacteremia in children with acute lymphoblastic leukemia. 836 63

Acute respiratory failure (ARF) is a typical complication of chemotherapy for hematologic malignancies. Despite the effective correction of gas exchange by mechanical ventilation, the mortality in this population is expected to be extremely high due to unavoidable fatal infection of immunocompromised host and the poor prognosis of primary malignancy. However, modern specific treatment of leukemia and lymphoma has made these conditions curable in many cases, and even severe myelotoxic neutropenia does not always lead to uniformly fatal outcome. We studied survival in 113 cases of ARF retrospectively selected according to the uniform criteria of this syndrome. No selection was made as to the diagnosis, stage, and response to the treatment of the underlying disease. The group consisted of 51% male and 49% female patients aged 34, on an average; 69% of these with acute leukemia, 22% with malignant lymphoma, and 9% with other conditions. Sixty-five (58%) patients were subjected to mechanical ventilation (MV). Forty-two were treated after a Protocol on intensive care of ARF which contained standard requirements to management of patients. Another group of 71 patients admitted to intensive care units before this Protocol was introduced were historical controls. Total survival was 19.5%. In the MV group survival was 15% with 10 cases of cure, ARF developing during severe neutropenia in 3 out of these 10 cases. The results became evidently better after the Protocol was introduced, improving from 16 to 27%. The primary disease dramatically influenced the results: long-term survival was significantly poorer in patients with relapses and resistant to chemotherapy, with 100% mortality within 8 months after discharge. A conclusion is drawn that intensive care of ARF including MV is justified in patients with hematologic malignancies, except cases when primary malignancy is not properly treated or resistant to specific chemotherapy.
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PMID:[Acute respiratory insufficiency in hemoblastoses: evaluation of treatment effectiveness by survival rate]. 853 69

The use of hematopoietic growth factors (HGFs) in the allogeneic transplant setting has sometimes been avoided for fear of stimulating leukemic cell growth and intensifying graft-vs.-host disease (GVHD). However, neither an increase in relapse rate nor an aggravation of GVHD has been routinely described when HGFs are used after allogeneic bone marrow transplantation (allo-BMT). Early outcomes after HLA-matched allo-BMT in 26 patients with hematologic malignancies treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) from the day of transplantation were analyzed. Results were compared to those from a series of 38 patients treated earlier with an identical approach, but not scheduled to receive HGFs after transplantation. All patients received a preparative regimen consisting of etoposide, cyclophosphamide, and total-body irradiation and GVHD prophylaxis with cyclosporine and a short course of methotrexate (MTX). The analysis has shown that the duration of neutropenia was significantly decreased in the group of patients treated routinely with HGFs (median 17 vs. 20 days; p < 0.001). These patients also required fewer days of intravenous antibiotic therapy (median 20 vs. 34 days; p < 0.001), had fewer positive blood and tissue cultures (median 2 vs. 12 and 13 vs. 28; p = 0.02 and p = 0.05, respectively), needed fewer packed red blood cell transfusions (median 7 vs. 11; p < 0.03), and were discharged earlier from the hospital (median 33.5 vs. 39 days; p < 0.001). The use of HGFs was not associated with an increase in acute GVHD or early leukemic relapse. No side effects were attributable to the simultaneous administration of MTX and HGF during the neutropenic period. A trend toward better 100-day actuarial survival for patients treated with rhG-CSF or rhGM-CSF did not reach statistical significance. A decrease in the number of early deaths from fungal or bacterial infections was found in the cytokine-treated group (p = 0.05). These data suggest that the early use of rhG-CSF or rhGM-CSF after HLA-matched allo-BMT in hematologic malignancies accelerates engraftment, reduces hospitalization time, and improves outcome, without increasing acute GVHD or early relapse. Because MTX-based prophylaxis regimens are associated with prolonged neutropenia, the routine use of HGFs after transplantation may be particularly useful in regimens including MTX.
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PMID:Hematopoietic growth factors after HLA-identical allogeneic bone marrow transplantation in patients treated with methotrexate-containing graft-vs.-host disease prophylaxis. 854 38

Fifty febrile episodes in patients with hepatobiliary and pancreatic cancer were reviewed. Biliary obstruction often resulting in cholangitis was an important predisposing factor, whereas neutropenia (< 500 PMN/mm3) was uncommon (10%). Microbiologically documented infections originating from the gastrointestinal tract were predominant, with Enterococcus faecalis and Escherichia coli being isolated most often. Non-infectious causes of fever occurred in 16% of patients. Only one patient developed a fungal infection. The overall response rate to therapy was 94%, with 32% being eligible for outpatient management. These data are quite different from those generated from patients with hematologic malignancies and indicate that disease-site specific management guidelines need to be developed for febrile episodes in patients with various underlying neoplasms.
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PMID:Nature and outcome of febrile episodes in patients with pancreatic and hepatobiliary cancer. 856 41

The clinical charts of cancer patients with documented fungal infections hospitalized at G. Gaslini Children's Hospital, Italy, from 1980 to 1990 were reviewed. Thirty-seven episodes developing in 37 patients were identified, based on microbiological and/or histological documentation. Patients' age ranged from 3 months to 18 years (median 7 years). Twenty patients were treated for hematological malignancy and 17 had solid tumor. Seven patients (3 with leukemia and 4 with solid tumours), developed mycosis after bone marrow transplantation procedure. A history of neutropenia in the month preceding the documentation of fungal infection was present in 76% of cases (28 of 37). However, only 16 of 28 (55%) of these patients were still neutropenic at time of diagnosis. In 40% of the cases the fungal infection developed as primary infection not preceded by any febrile and/or infectious episode. Fungemias without evident organ localization accounted for the 40% of episodes with a mortality rate of 20%. The other 22 cases (60%) were classified as invasive mycoses; 9 of these patients died (41%). Mortality was higher among patients with mold infection (5 of 7, 72%), than in those with yeast infection (7 of 29.24%). Molds infections and invasive mycoses were virtually absent in the first part of our period of observation (1980-84), but emerged in the second period (1985-90) when also the incidence rate of fungal disease increased (from 2.67/10,000 person/day to 5.93), probably in relation with extensive construction works and with the implementation of a bone marrow transplantation program.
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PMID:[Fungal infections in pediatric oncology]. 868

Myelosuppression is the most common toxicity associated with the administration of dose-intensive cytotoxic chemotherapy. The basic understanding of neutrophil biology and the physiology of chemotherapy-induced neutropenia has advanced tremendously in the past 2 decades. Concordantly, the ability to reduce the morbidity associated with neutropenia has improved. Adjunctive cytokine and progenitor cell support of hematologic recovery after myelosuppressive therapy have proved to be models of translational research and have led to novel therapeutic initiatives for patients with cancer and hematologic malignancies. In this article, fundamental aspects of neutrophil production are discussed, and the clinical development of hematopoietic cytokines active on cells of the leukocyte lineages is presented.
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PMID:Chemotherapy and neutropenia. 870 61


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