Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixty-five patients with haematological malignancy received high-dose chemotherapy or chemoradiotherapy followed by a T replete, HLA-identical sibling bone marrow transplant. All were scheduled to receive a standard cyclosporine/methotrexate immune suppressive regimen to minimise the risk of graft-versus-host disease post-transplant. Forty-six patients received all four scheduled doses of methotrexate, while in nineteen the day 11 dose was omitted due to marked oropharyngeal mucositis or febrile neutropenia. There was a slight increase in the incidence of acute graft-versus-host disease (GVHD) grades I-IV in those not receiving compared to those receiving day 11 methotrexate (84 vs 71% (P = 0.04)). However, there was no difference in the incidence of acute GVHD grades II-IV (14 vs 22%), in the incidence of chronic GVHD (38 vs 47%), in transplant-related mortality (21 vs 24%), in relapse rate (42 vs 51%), in 4-year survival (38 vs 48%), or in disease-free survival (38 vs 42%). These findings suggest that the day 11 methotrexate dose could be omitted without a major deleterious effect on the outcome of HLA-identical sibling marrow transplantation.
 ...
PMID:Omission of day 11 methotrexate does not appear to influence the incidence of moderate to severe acute graft-versus-host disease, chronic graft-versus-host disease, relapse rate or survival after HLA-identical sibling bone marrow transplantation. 875 Feb 65

We undertook a retrospective review of all patients with hematologic malignancies in whom candidemia developed during chemotherapy-induced neutropenia in 1989 and 1990. Candidemia developed in 11 patients; five were receiving therapeutic doses of amphotericin B at the time of infection. Disseminated infection occurred in 2 of 5 patients with breakthrough infection and 3 of 6 patients with candidemia before receipt of amphotericin B. Among patients with breakthrough candidemia there was a trend toward more-prolonged neutropenia prior to infection (P = .069), but otherwise they were indistinguishable from other candidemic patients with regard to risk factors for candidemia. Amphotericin B-susceptible Candida albicans was isolated from two patients and Candida krusei from three patients with breakthrough infection. All patients were treated with amphotericin B; all breakthrough infections responded to treatment. Neutropenic patients with breakthrough candidemia were clinically similar to those whose candidemia preceded amphotericin B therapy, and there was no increase in morbidity and mortality among individuals with breakthrough infection.
 ...
PMID:Failure of systemic empirical treatment with amphotericin B to prevent candidemia in neutropenic patients with cancer. 885 63

The purpose of this study was to compare two different in vitro culture conditions for the preservation of human granulocytes. These cells could be used in patients with severe neutropenia following cytotoxic chemotherapy if the functional capacity was retained, and autologous transfusions of granulocytes would circumvent the risk of alloimmunization. Granulocytes were obtained from the peripheral blood of healthy donors and patients with hematologic malignancies who received cytotoxic chemotherapy supported by recombinant human granulocyte colony-stimulating factor (R-metHuG-CSF, 300 micrograms/day, s.c.). Granulocytes were either cultured for 72 h at 4 degrees C in the presence of 100 ng/ml G-CSF or cryopreserved at -196 degrees C. The viability, surface antigen expression, and function of the granulocytes were assessed. Since effective microbial killing involves the attachment of granulocytes to blood vessel walls, transmigration into tissues, chemotaxis, and phagocytosis, the surface expression of the adhesion molecules LFA-1 (CD11a/CD18) and gp 150,95 (CD11c/CD18) was measured. In addition, the IgG receptors Fc gamma RI (CD64), Fc gamma RII (CD32), and Fc gamma RIII (CD16), as well as the complement receptor CR3 (CD11b/CD18), were assessed. Dynamic superoxide anion release served as a measure of the metabolic pathway of the oxidative burst after f-Met-Leu-Phe (fMLP) and phorbol-12-myristate-13-acetate (PMA) stimulation. Substantial differences in the preservation of granulocyte integrity and function were observed between the two storage conditions. Cryopreservation abolished reactivity to extracellular stimuli and severely affected the cell phenotype. On the other hand, functional activity could be maintained for up to 72 h when in vivo primed granulocytes of patients were incubated at 4 degrees C in the presence of G-CSF. This storage modality may permit the use of granulocyte autotransfusion to reduce the risk of neutropenic fever.
 ...
PMID:Granulocytes harvested following G-CSF-enhanced leukocyte recovery retain their functional capacity during in vitro culture for 72 hours. 887 10

Prolonged thrombocytopenia is a frequent clinical problem in cancer patients undergoing high-dose chemotherapy and autologous transplantation. The use of GM-CSF as an adjuvant to autologous bone marrow transplantation (ABMT) has significantly reduced the duration of neutropenia after high-dose chemotherapy but failed to accelerate platelet recovery in transplanted patients. The more rapid hematopoietic reconstitution obtained by autologous mobilized peripheral blood progenitor cell transplantation (PBPCT) after high-dose chemotherapy has resulted in its increasing use instead of ABMT. However, PBPCT does not always produce faster platelet engraftment after high-dose chemotherapy, and persistent thrombocytopenia remains a significant clinical problem in PBPC-transplanted patients. The duration of severe thrombocytopenia (requiring frequent platelet transfusions) until platelet recovery varies widely depending on the quality of the autograft and previous radiotherapy or chemotherapy. The median days to reach 20,000/microliters platelets ranged from 10 to 32 days. Pilot clinical studies in which cancer patients were transplanted with enriched CD34+ cell autografts, obtained from G-CSF-mobilized PB, showed a similar platelet recovery after high-dose chemotherapy but also wide variation among the patients. The median days to reach 20,000/microliters platelets ranged from 9 to 38 days. The dose of CFU-GM in the autograft has been identified as the best predictive factor for hematopoietic recovery (p < 0.0001) after high-dose chemotherapy and autologous PBPCT in 118 patients with hematologic malignancies. A similar assessment of the megakaryocyte progenitor cells (BFU-MK and CFU-MK) in the autograft not only could predict time to platelet recovery but also could help to optimize the number and method of mobilization of the PBPC required to shorten the problematic obligatory 2-week duration of thrombocytopenia after high-dose chemotherapy. A routine assessment of the number of BFU-MK and CFU-MK present in each autograft and correlation with platelet recovery after transplantation would enable us to define the clinical threshold cell dose required for rapid platelet recovery. Recently, several non-specific cytokines with thrombopoietic activity have been evaluated in phase I clinical trials, including interleukin-1, interleukin-3 followed by GM-CSF, interleukin-6, and interleukin-11 in cancer patients, showing an encouraging trend toward a decrease in thrombocytopenia after chemotherapy. The recently cloned specific platelet cytokine, thrombopoietin, is currently undergoing phase I clinical studies, and the results are awaited with interest.
 ...
PMID:Thrombocytopenia after high-dose chemotherapy and autologous stem cell transplantation: an unresolved problem and possible approaches to resolve it. 887 16

We conducted a randomized multicenter study to compare the efficacy and safety of two antibiotic regimens (cefepime [2 g b.i.d.] plus amikacin or ceftazidime [2 g t.i.d.] plus amikacin) as first-line therapy for fever in patients with hematologic malignancies and neutropenia. A total of 353 patients were randomized according to a 2:1 (cefepime:ceftazidime) ratio. Two hundred-twelve patients in the cefepime group and 107 in the ceftazidime group (90% of all patients) were evaluable for efficacy. The polymorphonuclear neutrophil count was < 100/mm3 on enrollment for 70% of the patients. The mean duration of neutropenia was 26 days. The efficacy in both study arms was comparable, although a trend in favor of cefepime was seen in terms of therapeutic success (response rate, 27% vs. 21% for the ceftazidime group). The overall response rate after glycopeptides were added to the regimens was 60% for the cefepime group and 51% for the ceftazidime group; the bacterial eradication rates were 81% vs. 76%, respectively, and the rates of new bacterial infections were 14% vs. 18%, respectively. We conclude that the combination cefepime/amikacin is at least as effective as the reference regimen of ceftazidime/amikacin in this setting.
 ...
PMID:Cefepime/amikacin versus ceftazidime/amikacin as empirical therapy for febrile episodes in neutropenic patients: a comparative study. The French Cefepime Study Group. 899 54

The standard of therapy for the high risk adult neutropenic host being treated with broad spectrum antibiotics for fever has been to continue intravenous antibiotics until neutropenia resolves. We performed a small, limited pilot study to determine if it is safe to switch these patients to oral monotherapy with ciprofloxacin. Ten patients with hematologic malignancies who had < or = 108 granulocytes/mm3 after cytoreductive therapy and were afebrile for at least five days had intravenous antibiotics discontinued and were placed on oral ciprofloxacin. Eight patients were able to be discharged from the hospital and seven were treated without the need for reinstitution of intravenous therapy. Of the three failures, one developed fever with a new bloodstream infection and two developed fever with relapse of leukemia. Patients remained on ciprofloxacin an average of 14.5 days (range 4 to 35 days). Aggregate cost savings for the 10 patients from this approach were estimated to be $11,400 for antibiotics and $88,800 for hospitalization. If corroborated in larger, randomized studies, the use of "stepdown monotherapy" may be a cost effective approach to the management of the stable neutropenic patient.
 ...
PMID:Stepdown single agent antibiotic therapy for the management of the high risk neutropenic adult with hematologic malignancies. 902

Five hundred two central venous catheters inserted in 366 patients were evaluated prospectively over a one-year period to determine the frequency and risk factors associated with catheter-related sepsis. For study purposes, in cases in which catheter infection was suspected but the initial blood cultures were negative, the catheters were replaced by guidewire technique; otherwise, the catheters were routinely changed after 21 days by guidewire technique. A catheter-related infection was suspected in 190 cases (190/502, 38%). A diagnosis of catheter-related sepsis was established in 50 patients, which represents 10% of the total number of lines (502). Over a total of 6428 days of catheter use, the infection rate was 0.8 cases of sepsis per 100 catheter-days. Staphylococcus epidermidis, Staphylococcus aureus, and Candida spp. were the most frequently isolated aetiological agents of sepsis. On univariate analysis, six variables affecting the rate of catheter-related sepsis were identified: neutropenia for more than eight days (p < 0.001); AIDS (p < 0.001); haematological malignancy (p < 0.001); administration of total parenteral nutrition (p = 0.001); duration of site use (p = 0.04); and high APACHE II score (p = 0.04). The logistic regression analysis revealed that AIDS and haematological malignancies were independent risk factors of catheter-related sepsis. Catheter replacement over a guidewire was no more likely to be associated with sepsis than was percutaneous catheter insertion. In conclusion, although the incidence of established catheter infection is much lower than the incidence of suspected infection, in most cases of suspected infection it is wise to change the catheter with the guidewire technique and wait for culture of the tip, rather than to remove the catheter immediately. Such a policy may help reduce the number of unnecessary catheter removals.
 ...
PMID:Central venous catheter-related sepsis in a cohort of 366 hospitalised patients. 913 22

To identify the risk factors and attributable mortality associated with superinfections in febrile neutropenic patients with hematologic malignancies, we prospectively evaluated 333 episodes of fever and neutropenia by means of univariate and multivariate analyses. Superinfection was defined as any infection either occurring during antibiotic therapy or developing within 1 week after discontinuation of antibiotic therapy. Of 333 episodes, 46 (13.8%) were defined as superinfection; these episodes occurred in 46 patients. The risk factors for superinfection in the multivariate analysis were longer duration of profound neutropenia (P < .0001), lack of use of quinolones as prophylaxis (P < .0001), presence of a central venous catheter (P = .02), and persistence of fever after 3 days of antibiotic therapy (P = .02). The crude mortality rate among patients with superinfection was 48%, and the attributable mortality rate was 24% (95% confidence interval, 3%-45%). Identifying risk factors for superinfections in neutropenic patients might allow clinical practices to reduce the negative impact of this complication.
 ...
PMID:Risk factors and attributable mortality associated with superinfections in neutropenic patients with cancer. 914 30

Despite increasing reports of life-threatening Fusarium infections, little is known about its pathogenesis and management. To evaluate the epidemiology, clinicopathologic features, and outcome of invasive fusariosis in patients with hematologic cancer, we conducted a retrospective study of invasive fusarial infections in patients with hematologic malignancy treated at a referral cancer center over a 10-year period (1986 to 1995), as well as a literature review. Forty patients with disseminated and three patients with invasive lung infection were included in the analysis. All patients were immunocompromised. The infection occurred in three patients postengraftment following bone marrow transplantation. All patients were diagnosed antemortem. Thirteen patients responded to therapy, but the infection relapsed in two of them. Response was associated with granulocyte transfusions, amphotericin B lipid formulations (four patients each), and an investigational triazole (two patients). Resolution of infection was only seen in patients who ultimately recovered from myelosuppression. Portal of entry was the skin (33%), the sinopulmonary tree (30%), and unknown (37%). Fusarium causes serious morbidity and mortality, and may mimic aspergillosis. The infection seems to respond to newer therapeutic approaches, but only in patients with ultimate recovery from myelosuppression, and it may relapse if neutropenia recurs.
 ...
PMID:Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years' experience at a cancer center and implications for management. 924 29

The efficacy of piperacillin-tazobactam as first line empiric therapy was assessed in 54 febrile neutropenic episodes in 42 patients (27 male, 15 female) with haematological malignancy. Nineteen (35%) episodes were bacteraemias (15 Gram-positive, 4 Gram-negative), 5 (9%) were clinically documented (Hickman line sites) and 30 (56%) were pyrexias of unknown origin. Study therapy was initiated after a median of 4 days of neutropenia (range 1-30). Eighteen (33%) episodes responded to piperacillin-tazobactam without a need for treatment modification. Four (7%) episodes initially responded to piperacillin-tazobactam but required treatment modification for fungal superinfection. Of the 19 bacteraemias, 6 (32%) were eradicated or presumed eradicated by piperacillin-tazobactam. Of the 32 (60%) episodes which failed to respond to piperacillin-tazobactam, 11 (34%) responded to anti-fungal therapy; 14 (44%) responded to a glycopeptide and 5 (16%) responded to a second-line broad spectrum antibacterial agent. Two (6%) patients died, both in the presence of progressive malignancy. There was no significant toxicity associated with piperacillin-tazobactam. We conclude that piperacillin-tazobactam is effective as empiric monotherapy in neutropenic fever and may reduce the requirement for glycopeptides.
 ...
PMID:Piperacillin-tazobactam as empiric monotherapy in febrile neutropenic patients with haematological malignancies. 926 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>