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 use of high-dose chemotherapy and the subsequent prolonged neutropenia in patients with haematological diseases has resulted in an increased incidence of fungal infections. The diagnosis and treatment of these infections in neutropenic patients pose major therapeutic problems. The only drug with proven efficacy in the treatment of deep-seated fungal infections, including invasive aspergillosis, is amphotericin B. Unfortunately, this drug has adverse side effects, most importantly dose-dependent nephrotoxicity; furthermore, some patients fail to show a response to amphotericin B. We have treated 20 patients undergoing myeloablative chemotherapy and/or bone marrow transplantation for haematological diseases with liposomal amphotericin (AmBisome) for proven or suspected aspergillosis. Eighteen patients had diffuse interstitial pneumonitis and two patients had suspected fungal liver abscesses. Five patients had mycologically proven fungal infection and of these, three patients (60%) showed a complete response to liposomal amphotericin. Eleven patients received liposomal amphotericin because of the failure of conventional amphotericin B to eradicate proven or suspected fungal infection. Five of these 11 patients (45%) showed a complete clinical response to liposomal amphotericin. Eight patients received liposomal amphotericin because of pre-existing renal impairment or nephrotoxicity caused by conventional amphotericin B. Four of these patients (50%) showed a response to liposomal amphotericin. Recovery from probable fungal infection in this group of patients occurred when there was complete remission of underlying disease and recovery of neutrophil counts, when they were concurrently treated with liposomal amphotericin.
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PMID:Liposomal amphotericin B (AmBisome) in the treatment of fungal infections in neutropenic patients. 177 96

We performed clinicopathological studies on early-onset sepsis (5 infants, less than 72 hours of life, EOS) and late-onset sepsis (15 infants, greater than 72 hours, LOS) of very low birth weight, less than 1500 g (VLBW). In EOS, the clinical features mimic the respiratory distress syndrome and hematological changes were not observed. The lungs showed slight interstitial pneumonia with structural immaturity, hyaline membranes, hemorrhage, and minimal infiltration by polymorphonuclear neutrophils (PMNs). The pathogen was group B streptococcus or weakly gram-negative bacilli. In LOS, pneumonia proceeded to sepsis and neutropenia with elevated numbers of circulating immature neutrophils, and increased levels of C-reactive protein were observed at the onset of sepsis. Severe pneumonia with infiltration of numerous PMNs and bacterial colonies and polymicrobial infection by nosocomial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa were common. The thymus and spleen weights varied but retained normal structure in EOS. The thymus was depleted of lymphocytes, and the spleen was hypertrophic but poorly reactive against infection in LOS. The pathogenesis of EOS is regarded as being more closely correlated with lung immaturity and circulatory disorder in early life, whereas that of LOS is associated with immunological defenses of the host, potency of the pathogens, and terminal multiple organ failure.
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PMID:Clinicopathological differences between early-onset and late-onset sepsis and pneumonia in very low birth weight infants. 223 61

This study included 44 children undergoing autologous marrow transplantation for leukemia between August 1979 and June 1987. Three of them received a second transplant. In the phase of neutropenia, 38 children presented with fever. Nineteen septicemia occurred (13 Gram positive cocci, 6 Gram negative bacteria), and 2 interstitial pneumonitis were observed. All children with documented infection or a fever of unknown origin recovered after treatment, except 3, who died from infection. The latest antimicrobial therapy used was a combination of an aminoglycoside and a third generation cephalosporin. When necessary, vancomycin or amphotericin B were added. After engraftment (granulocyte count greater than 0.5 X 10(9)/l) 14 septicemia (which recovered) and 10 herpes zoster infections were observed. Only one patient died of infection (herpes zoster with encephalitis).
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PMID:[Infections and bone marrow autograft carried out for leukemias in children. Apropos of 47 cases]. 306 29

Aspergillus infection was studied in patients admitted to the Bone Marrow Transplant (BMT) Service at the Johns Hopkins Oncology Center during a 9-year period. The overall incidence was 4% in 549 patients reviewed. The incidence at autopsy was 12% (21 of 174 patients autopsied). There was no difference in frequency of occurrence in allogeneic compared to autologous BMT recipients. However, all infections in autologous BMT patients (5 of 5) occurred during neutropenia before engraftment. In contrast, 16 of 17 infections in allogeneic BMT patients occurred after engraftment (p = 0.0002). This difference presumably related to differences in duration of neutropenia and immunodeficiency. Age, underlying disease, date of BMT, preparative regimen, remission status, prior treatment, interstitial pneumonitis and concomitant cytomegalovirus infection did not predispose patients to aspergillus infection. Different post-BMT immunosuppressive regimens did not affect the risk for aspergillus infection except that patients who were given cyclophosphamide plus methylprednisolone had a higher incidence of aspergillus infection than those given methotrexate (12% versus 1%, p = 0.03). Acute graft-versus-host disease imposed a slight risk for infection (p = 0.06).
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PMID:Aspergillus infections in bone marrow transplant recipients. 333 65

Autopsies were performed on 2 patients with aplastic anaemia and 7 with acute leukaemia dying after bone marrow transplantation. Neutropenic enterocolitis was found in 2 of the 3 early deaths occurring before marrow engraftment and was related to radiation or cytotoxic drug damage to the bowel mucosa in the presence of profound neutropenia, allowing infection by bowel organisms. Cytomegaloviral infection was universal in engrafted patients. One had cytomegaloviral (CMV) pneumonia, one CMV hepatitis and enteritis and one CMV enteritis. Three patients had occasional CMV inclusions in various organs without obvious harmful effects. One nonengrafted patient also had CMV pneumonia. Graft versus host disease (GVHD) was a significant finding in 4 engrafted patients. This was difficult to separate histologically from the effects of CMV in the bowel, but easier in liver and skin. The skin changes of GVHD were the most easily interpretable. Interstitial pneumonia was due to CMV in one nonengrafted and one engrafted patients and had no obvious infective cause in 2 engrafted patients. The presence of bizarre epithelial cells in the lungs of these patients suggested an aetiological role for radiation or cytotoxic drugs. Modification of the conditioning regimen may reduce tissue damage and lessen many of these side-effects.
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PMID:Autopsy findings in bone marrow transplantation. 628 56

Several clinical trials have demonstrated that granulocyte colony-stimulating factor (G-CSF) accelerates the recovery of neutropenia in chemotherapy-induced bone marrow suppression. In this report, we describe a 46-year-old female with glioblastoma multiforme who developed interstitial pneumonia due to administration of G-CSF during the phase of immunochemoradiotherapy-induced neutropenia. Thirty-three days after starting immunochemoradiotherapy (ACNU, VCR, IFN -beta, radiation), she developed neutropenia (1,000/microliters). Administration of G-CSF at doses of 125-250 micrograms/day led to an increase of peripheral neutrophil counts. Eleven days later, the patient developed sudden severe respiratory failure and cyanosis with worsening of lung shadows. Blood gas levels on room air were PaO2 49.3mmHg, PaCO2 28.0mmHg, and pH 7.46. At this time, her neutrophil count had risen to 26,080/microliters. LDH and alpha - HBD had also increased to 1,439 IU/l and 1,117IU/l respectively. Chest radiograph and CT scan demonstrated interstitial pneumonia. After treatment with methyl prednisolone, her respiratory symptoms were gradually resolved. A number of side-effects have been reported with granulocyte-macrophage colony-stimulating factor (GM-CSF). These include fluid retention with pericardial and pleural effusion, fever, bone pain, fatigue, and rash. This report also suggests that G-CSF might be a cause of interstitial pneumonia during the phase of immunochemoradiotherapy-induced neutropenia.
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PMID:[A case report of interstitial pneumonia caused by granulocyte colony-stimulating factor]. 750 62

The purpose of this trial was to evaluate the efficacy and the tolerance of high-dose therapy with autologous stem cell transplantation as part of front-line therapy in Hodgkin's disease for patients with both adverse prognostic factors: high tumor burden at presentation and slow response to initial chemotherapy. In a prospective one-center study, 20 consecutive patients with slow response (tumor reduction < 75%) (16 pts) or refractory (4 pts) to 3-4 courses of conventional HD chemotherapy received high-dose therapy followed with autologous bone marrow (14 pts) or peripheral blood stem cell (6 pts) transplantation. They were 13 males, 7 females, median age 26 years (8-45). At the time of initial diagnosis, all but one of the patients had B symptoms, all had high-risk HD defined as Ann Arbor stage IV (7 pts) or large mediastinal involvement (LMI = tumor/thorax > 0.45 at T5-T6) (6 pts) or both stage IV+LMI (7 pts). Median time between diagnosis and autotransplantation was 5 months. Intensive therapy consisted of either CBV (cyclophosphamide 1.5 g/m2 x 4, BCNU 300 mg/m2, etoposide 200 mg/m2 x 3) (12 pts) or cyclophosphamide 120 mg/kg + 12 Gy total body irradiation for 8 patients with diffuse bone or lung involvement. For pts treated with CBV, 40 Gy involved field radio-therapy was performed after hematological recovery. Median duration of neutropenia was 16 days (9-21). Neither veno-occlusive disease, nor interstitial pneumonitis nor toxic death were observed. Seventeen pts are alive with no progression of the disease (16/16 in partial response after initial chemotherapy, 1/4 with refractory disease).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early intensive therapy with autotransplantation for high-risk Hodgkin's disease. 751 54

A late Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in previously untreated patients with non-small cell lung cancer was jointly carried out in 26 medical institutions. Of 80 enrolled cases, 75 cases were eligible, and PR was attained in 23 cases (30.7%). The main adverse effect of this drug, leukopenia (neutropenia), was observed in 62.7% (83.3%) of Grade 3 and 4 cases, but they recovered rapidly. In addition to decreased hemoglobin in 67% (Grade 3 in 5.7%) of the cases, adverse effects included slight disorder of hepatic function, anorexia, nausea and vomiting, fever, general fatigue, phlebitis, paresthesia and interstitial pneumonia. Peripheral neuropathy such as paresthesia occurred rarely and was slight, if any.
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PMID:[Late phase II clinical study of KW-2307 in previously untreated patients with non-small cell lung cancer. KW-2307 Study Group (Lung Cancer Group)]. 808 45

Pulmonary toxicity occurs in approximately 10 to 50% of patients undergoing bone marrow transplantation (BMT). Bacterial pneumonia very commonly affects patients within the first 6 months post-BMT. Etiologic factors include neutropenia and the presence of graft-versus-host disease (GVHD). Pulmonary fungal infections, due to candida and aspergillus, may develop in 16% of patients receiving BMT, with a high mortality rate, being about 80%. A prolonged neutropenia as well as GVHD and associated immunosuppressive treatments are important factors in predisposing a patient to develop fungal pneumonitis. Interstitial pneumonitis occurs in 10-40% of patients; herpes viruses are the most commonly documented cause, with cytomegalovirus (CMV) being the most common pathogen. No causative organism is identified in up to 60% of the cases. It is likely that some of these cases may result from drug or radiation toxicity. Lung shielding and fractionation of the dose have decreased the incidence of interstitial pneumonitis to less than 5%. Patients with GVHD are predisposed to lung infections because of the immunosuppression that accompanies GVHD and its treatment. In addition, GVHD itself appears to have a direct effect on pulmonary epithelium. Cultural and serologic studies as well as radiographic investigations and other diagnostic procedures (ie bronchoalveolar lavage) are needed for appropriate management of pulmonary complications.
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PMID:[Pulmonary complications after bone marrow transplantation]. 835 44

We evaluated the efficacy of ganciclovir to prevent the development of cytomegalovirus interstitial pneumonitis (CMV-IP) in patients with bone marrow transplants. Of 35 patients enrolled in this study, 33 were seropositive for CMV or had seropositive donors, and two were seronegative before transplant but were positive for CMV examined by polymerase chain reaction (PCR) on days 30-37. Ganciclovir was given at a dose of 250 mg/body daily from day 30-37 to day 70. Blood, throat swabs, urine and bronchoalveolar-lavage fluid (BALF) were screened for CMV by PCR on days 30-37, 70 and 100. CVM-IP developed in two of 35 patients (5.7%) who received ganciclovir for prophylaxis, as compared with six of 39 historical controls who did not receive ganciclovir. A significant reduction of CMV detection by PCR in blood, throat swabs, and BALF was observed after administration of ganciclovir, on day 70. The incidence of neutropenia, thrombopenia and renal impairment in the study period showed no difference between the study group and the historical control. Early prophylactic use of ganciclovir appears to reduce the risk of CMV disease in allogeneic transplant recipients with positive serology or positive CMV-PCR.
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PMID:[Ganciclovir prophylaxis for cytomegalovirus interstitial pneumonitis after allogeneic bone marrow transplantation]. 868 62


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