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)

Ninety-two AIDS patients with Pneumocystis carinii pneumonia (PCP) were randomized to receive folinic acid or matching placebo in conjunction with trimethoprim-sulfamethoxazole in a prospective, double-blind trial. Neither frequency of dose-limiting toxicity (26% vs. 37%; P = .4) nor time to occurrence (P = .7) was associated with folinic acid use. Although incidence of neutropenia was lower in patients receiving folinic acid (23% vs. 47%; P = .03), time to occurrence of neutropenia did not differ (P = .4). Seven (7.6%) of 92 patients with confirmed PCP met criteria for therapeutic failure, and 5 (6%) died during therapy. Surprisingly, folinic acid use was associated with a higher rate of both therapeutic failure (15% vs. 0; P = .01) and death (11% vs. 0; P = .06). Time to therapeutic failure was shorter and probability of death greater in patients receiving folinic acid (P = .005, P = .02, respectively), even when adjusted for baseline arterial oxygen pressure, serum lactate dehydrogenase, respiratory rate, CD4 cell count, and peak serum level of trimethoprim or sulfamethoxazole.
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PMID:Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. 793 Jul 36

An intensive chemotherapy regimen (EVDAC), including high-dose epirubicin, vincristine, and dexamethasone followed by cyclophosphamide and high-dose cytarabine, was administered to 54 untreated adults with intermediate or high-grade non-Hodgkin's lymphomas (NHL). The median age was 59, 61% were Ann Arbor Stage IV, 57% had "B" symptoms, 50% had serum lactate dehydrogenase greater than 250 U/L, and 48% had masses greater than 7 cm (33% > 10 cm) in diameter. Seventy-six percent of patients attained complete or probable complete remissions. The Kaplan-Meier actuarial failure-free survival at 7 years is 50%, and 59% (32 of 54) of all patients started on therapy remain alive and in first remission at a median of 62+ (range, 49+ to 76+) months from completion of therapy. Nearly all patients developed severe neutropenia. Febrile episodes requiring hospitalization during neutropenia occurred after 56% of courses of epirubicin, vincristine, and dexamethasone and after 9% of courses of cyclophosphamide and cytarabine; 80% of patients were hospitalized at least once. Platelet count nadirs of less than 20,000/microL occurred after only 1 of 146 evaluable courses of epirubicin and after none of the cyclophosphamide/cytarabine courses. Although 8 patients had decreases of at least 0.12 in their left ventricular ejection fractions (5 to below normal levels), none have developed clinically evident congestive heart failure. Clinically significant mucositis occurred after only 8% of courses of high-dose epirubicin. Three deaths from infections and one from hyperkalemia with cardiac arrest occurred during therapy. These results confirm that high remission and sustained, failure-free survival rates can be achieved in patients with aggressive NHL, using high-dose anthracycline-containing chemotherapy regimens. Epirubicin appears to have an advantage over doxorubicin at high doses because of decreased toxicity at a therapeutically equivalent dose. These phase II study results need to be validated in a randomized phase III trial, and growth factors should be used to attempt to reduce the neutropenia-associated complications.
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PMID:Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with an intensive epirubicin-containing regimen. 826 Jun 95

We report the cases of six patients with AIDS in whom reactive hemophagocytic syndrome (RHPS) secondary to disseminated histoplasmosis was diagnosed. RHPS was diagnosed by established criteria, including fever (duration of > or = 7 days, with peak temperatures of > 38.5 degrees C), unexplained thrombocytopenia with anemia and/or neutropenia, and bone marrow biopsy findings of hemophagocytic histiocytosis. Disseminated Histoplasma capsulatum infection was diagnosed on the basis of the results of cultures of the bone marrow sample. The serum lactate dehydrogenase (LDH) level was elevated (> 1,000 IU/L) in all patients, and five of six patients had hyperferritinemia (range of ferritin level, 15,848-425,984 ng/mL). Five patients had features resembling severe sepsis with multiorgan dysfunction. Three patients recovered, and the findings of RHPS resolved following therapy with amphotericin B. In patients with AIDS, the combination of fever, cytopenia, elevated serum LDH level (> 1,000 IU/L), and/or hyperferritinemia (ferritin level of > 10,000 ng/mL) is a clue to the diagnosis of RHPS and disseminated histoplasmosis; bone marrow biopsy is valuable in establishing the diagnosis.
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PMID:Reactive hemophagocytic syndrome: a new presentation of disseminated histoplasmosis in patients with AIDS. 874 33

Pulmonary alvelolar proteinosis (PAP) is a rare cause of chronic respiratory failure due to progressive alveolar accumulation of a periodic acid-schiff (PAS) positive proteinaceous material. In some cases, the rapid accumulation of intra-alveolar material leads to acute respiratory failure (ARF). We report the causative role of secondary PAP in the case of a 26-year-old man with acute myeloid leukemia who developed fever, increased serum lactate dehydrogenase level and ARF, and required mechanical ventilation. The diagnosis of PAP was established by the examination of material obtained by bronchoalveolar lavage (BAL). Respiratory improvement occurred several days after the patient had recovered from neutropenia. This report underlines the importance of the early diagnosis of PAP as a potential cause of ARF in leukemic patients. Adequate stain on BAL fluid provides the diagnosis and avoids repeated invasive procedures and inappropriate treatments.
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PMID:Acute respiratory failure caused by secondary alveolar proteinosis in a patient with acute myeloid leukemia: a case report. 956 12

In an experimental study we measured changes in hematological, biochemical and cortisol parameters in 6-week-old Swiss mice continuously exposed to ELF generated by a transformer station and high current bus bars. Mean daily exposure of 5.0 microT was maintained for 350 days. Hematological parameters were compared to those of control mice (n=12) exposed to a field level lower than 0.1 microT. Serum biochemical parameters (sodium, potassium, chloride, calcium, magnesium, phosphorus, amylase, creatine phosphokinase, and lactate dehydrogenase) were measured after 28 days of exposure and serum cortisol after 90 and 190 days. Granulocyte/macrophage colony-forming cells (GM-CFC) were counted at the end of the 350-day exposure. On day 20, exposed animals showed a significant decrease in leukocyte, erythrocyte, lymphocyte and monocyte counts and in hemoglobin and hematocrit values, while MCV increased. On days 43 and 63 no significant difference was observed in leukocyte and erythrocyte values, as if hemopoiesis had recovered. On day 90, a significant fall in the leukocyte, polynuclear neutrophil and eosinophil counts was observed in the exposed animals. No significant difference was noted in the biochemical parameters studied. On day 190, exposed animals had neutropenia and a decrease in the cortisol value. On day 350, no significant difference in hematological parameters was noted. Individual differences in sensitivity were observed, as 8 mice in the exposed group showed a significant decrease in the leukocyte, polymorphonuclear neutrophil and GM-CFC counts, while in two mice there was a significant increase in these same values compared to those unexposed mice.
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PMID:Alterations of biological parameters in mice chronically exposed to low-frequency (50 Hz) electromagnetic fields. 957 Mar 42

Serum concentrations of hepatocyte growth factor (HGF) were measured in 60 patients suffering from acute myelocytic leukaemia (AML). At the time of diagnosis elevated HGF concentrations (> 1.25 ng/ml) were found in 28% of the patients. HGF levels correlated with the presence of disseminated intravascular coagulation (DIC), levels of lysozyme, creatinine, peripheral blood blast counts and lactic dehydrogenase. In the group of patients with high HGF (>1.25 ng/ml) we found a tendency towards an increased early mortality; 41% of them died within 15 d from diagnosis, as opposed to 5% of the patients with normal HGF (log rank test p=0.07). DIC-related bleeding or thrombosis contributed to this early mortality. In responders, HGF levels normalized after treatment. HGF levels are low in neutropenia and neutropenic infections.
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PMID:Elevated serum concentrations of hepatocyte growth factor in acute myelocytic leukaemia. 1005 17

We describe a case of T-cell large granular lymphocyte (LGL) leukaemia that transformed into a large-cell T-cell lymphoma 11 years from diagnosis. A 29-year-old asymptomatic female presented in 1989 with lymphocytosis, neutropenia and mild bone marrow infiltration. The circulating cells were LGL with a CD2+, CD3+, CD8+, CD4-, CD16+, CD56+, CD57- phenotype. In August 2000, she developed fever, a large submandibular mass and hepatosplenomegaly. Biochemistry showed abnormal liver function tests and raised lactate dehydrogenase (LDH) levels. A serological screen for Epstein-Barr virus, cytomegalovirus, human T-lymphotropic virus-I, human herpes virus (HHV)-6 and HHV-7 was negative. Histology of the mass was consistent with the diagnosis of peripheral T-cell lymphoma composed of large cells, and immunohistochemistry showed that the lymphoma cells had a phenotype identical to the mature LGL. Molecular analysis with the polymerase chain reaction (PCR) demonstrated rearrangement of the T-cell receptor (TCR) gamma-chain gene with a band of identical size in both bone marrow mature LGL and lymph node cells. The patient was treated with CHOP (cyclophosphamide, vincristine, doxorubicin and prednisolone), resulting in the disappearance of the mass and improvement of the hepatosplenomegaly, LDH and liver abnormalities. She underwent splenectomy, and spleen histology showed involvement by T-cell LGL leukaemia with no evidence of transformation. This case illustrates that transformation or Richter syndrome may occur in a minority of patients with T-cell LGL leukaemia, a disease that has a benign clinical course in most cases. This is the first case documented by molecular methods of the transformation of the pre-existing clone.
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PMID:Transformation of T-cell large granular lymphocyte leukaemia into a high-grade large T-cell lymphoma. 1184 12

Strategies for identifying patients at high risk of chemotherapy-induced neutropenia are reviewed. Among lung cancer patients, a 24% rate of neutropenia has been reported. This rate is below the 40% threshold recommended by the American Society of Clinical Oncology (ASCO) for the prophylactic use of colony-stimulating factors. Risk factors for febrile neutropenia in patients receiving adjuvant chemotherapy for breast cancer include older age, fluorouracil-containing regimens, bone marrow involvement or prior myelosuppressive therapy, and concomitant or prior radiation therapy. According to the Silber predictive model, factors suggesting a high risk of hospitalization for febrile neutropenia include the absolute neutrophil count during the neutrophil nadir in cycle 1 of chemotherapy. Patients with non-Hodgkin's lymphoma (NHL) are at risk of febrile neutropenia and fall on the edge of the ASCO guidelines. Risk factors in NHL patients include certain combination chemotherapy regimens, an albumin concentration of > 3.5 g/dL, an above-normal lactate dehydrogenase concentration, bone marrow involvement, age of > 65 years, and renal disease. Patients can be stratified into low-risk and high-risk categories for febrile neutropenia. High risk is associated with a duration of neutropenia of more than seven days and concomitant medical conditions, such as hypotension and diarrhea. A majority of low-risk patients can be managed as outpatients. Prophylactic use of colony-stimulating factors is currently believed not to be cost-effective if the frequency of febrile neutropenia is less than about 20% for a given treatment regimen. Patients at higher risk of febrile neutropenia in association with cancer chemotherapy may include the elderly and those with specific malignancies and prior neutropenic events, as well as those receiving combination chemotherapy and radiation therapy.
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PMID:Identification of cancer patients at high risk of febrile neutropenia. 1216 33

Numerous salvage protocols for relapsed or refractory aggressive non-Hodgkin's lymphomas have been described. The purpose of this retrospective study was to evaluate the efficacy and the toxicity of the ASHAP protocol, which combines a continuous infusion of doxorubicin and cisplatin with high-dose cytarabine and methylprednisolone. Twenty-four patients with relapsed or refractory aggressive non-Hodgkin's lymphomas were treated with a median of 3 cycles (range: 1-5) of ASHAP. Twelve patients achieved a complete and four a partial remission for an overall response rate of 67%. The 3-year overall and progression-free survival rates were 60% and 40%, respectively. Ten of the responding patients were consolidated by high-dose chemotherapy. After a median follow-up of 15.5 months, four patients are in continuous complete remission, while six patients suffered relapses (two fatal). For reasons of low risk profile [international prognostic index (IPI) score of 0, n=2] or age >60 years ( n=4), consolidation was limited to involved-field radiotherapy in six patients. All of these patients are alive after a median follow-up of 37 months, with two relapses. Factors predicting a poor response to salvage therapy were primary refractory disease, elevated lactate dehydrogenase activity, and an IPI score of >/=2. The principal toxicity was myelosuppression with grade III or IV neutropenia or thrombocytopenia occurring in 88% or 75%, respectively, of the patients. Nonhematological toxicity was generally mild. There were no treatment-related deaths. The ASHAP regimen is a highly active and well-tolerated salvage protocol for patients with relapsed aggressive non-Hodgkin's lymphomas which compares favorably with other established protocols.
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PMID:Salvage chemotherapy according to the ASHAP protocol: a single-center study of 24 patients with relapsed or refractory aggressive non-Hodgkin's lymphomas. 1291 Mar 75

Yondelis (ET-743) is a novel anticancer agent isolated from the marine ascidian Ecteinascidia turbinata. ET-743 possesses potent antitumour activity and a novel mechanism of action at the level of gene transcription. We conducted two sequential phase I dose escalation and pharmacokinetic studies of ET-743 given as a 1- or a 3-h intravenous (i.v.) infusion. Seventy-two adults with metastatic or advanced solid tumours received ET-743 in escalating doses between 50 and 1100 microg/m(2), initially as a 1-h infusion, and later at doses between 1000 and 1800 microg/m(2) as a 3-h infusion every 3 weeks. The maximum tolerated dose (MTD) of ET-743 was 1100 microg/m(2) for the 1-h infusion schedule and 1800 microg/m(2) when given as a 3-h infusion. Dose-limiting toxicities (DLTs) were fatigue, neutropenia and thrombocytopenia. Transient non-cumulatives grade 3-4 increase in transaminases (not considered DLT) and grades 3-4 nausea and vomiting were frequently observed. Other toxicities (maximum grade 3) included anaemia, increased lactate dehydrogenase (LDH), bilirubin and alkaline phosphatase serum levels, and phlebitis; there were no toxic deaths. One pCR (melanoma), CR (uterine leiomyosarcoma), one PR (colon stromal sarcoma) and a MR (37% tumour shrinkage, gastric stromal sarcoma) were observed. A further 9 patients with colorectal, mesothelioma, bile duct carcinoma and bladder cancer had SD which lasted for six or more treatment cycles. ET-743 pharmacokinetics were linear with the 3-h infusion schedule. The haematological and hepatic toxicities of ET-743 were dose-dependent and not cumulative. Based on the current trial, the recommended dose of ET-743 for phase II studies is 1650 microg/m(2) given as a 3-h infusion.
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PMID:Phase I and pharmacokinetic study of Yondelis (Ecteinascidin-743; ET-743) administered as an infusion over 1 h or 3 h every 21 days in patients with solid tumours. 1293 61


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