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)

Amikacin, a new aminoglycoside antibiotic, was utilized in the treatment of 49 cases of infection which occurred in 39 neutropenic cancer patients. Thirty-four patients (69 per cent) responded to this antibiotic. Pneumonia and septicemia were the most common types of infection treated and the response rates were 65 per cent and 75 per cent, respectively. Gram-negative bacili were responsible for 93 per cent of the identified infections and 74 per cent responded. E. coli, Ps. aeruginosa, and organisms of the Klebsiella-Enterobacter-Serratia group were the most common gram-negative bacilli causing infection. Responses were more frequent among patients who maintained higher serum concentrations of antibiotic, but the differences were not statistically significant. Patients with severe neutropenia (less than 100 neutrophils/mm3) had a response rate of 68 per cent. Toxicity was manifested as azotemia and hearing loss which occurred in 13 per cent and 6 per cent, respectively. However, toxicity was directly related to serum concentration and to the number of treatments with amikacin. This antibiotic is of potential importance because of its efficacy against gram-negative bacilli infections. Best results were obtained when sufficient drug was given as a continuous intravenous infusion to maintain serum concentrations of about 15 mu g/ml.
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PMID:Amikacin therapy of infections in neutropenic patients. 110 49

We describe the results of treatment with 2'-deoxycoformycin (DCF) in 68 patients with post-thymic (mature) T-cell malignancies. These included: prolymphocytic leukaemia (T-PLL), 31, HTLV-1 + adult T-cell leukaemia/lymphoma (ATLL), 20, cutaneous T-cell lymphoma (CTCL), comprising mycosis fungoides and Sezary syndrome, 13, and large granular lymphocytic leukaemia, four. Two-thirds of patients were refractory to previous therapy, which included four drug combinations. DCF was given intravenously at 4 mg m-2 weekly for the first 4 weeks and then every 2 weeks until maximal response. Toxicity was very low with only one death resulting from prolonged neutropenia. Overall response rates, partial (PR) and complete. (CR), were 38%, with variations according to diagnosis. Best responses, 54%, were seen in CTCL but limited to Sezary patients, one CR, six PR, whilst none of the mycosis fungoides responded. Responses in T-PLL were recorded in 48% including three CR (of 8-12 months' duration unmaintained) and 12 PR. Fifteen per cent of responses were seen in ATLL. The only ATLL responders - two CR, one PR - were those patients who received combination chemotherapy prior to DCF, with reduction of tumour bulk but short of PR. When results were analysed according to membrane phenotypes it was apparent that responses were seen mainly in cases with CD4+, CD8- T cells -22 of 47 (47%) - contrasting with only three of 19 (16%) with other T-cell phenotypes. We conclude that DCF is a useful therapy for the treatment of T-cell leukaemias, in particular Sezary syndrome and T-PLL, and should play a part in strategies to improve the natural history of this group of lymphoid malignancies.
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PMID:Deoxycoformycin in the treatment of mature T-cell leukaemias. 193 13

The utility of current chemotherapeutic regimens in the treatment of AIDS-related Kaposi's sarcoma (AIDS-KS) is often compromised by both limited efficacy and substantial toxicity. Pegylated (Stealth) liposomal doxorubicin hydrochloride (SL-DOX) has been demonstrated specifically to deliver high concentrations of doxorubicin to Kaposi's sarcoma (KS) lesions. This phase II study was performed to evaluate the efficacy and safety of SL-DOX in the treatment of moderate to severe AIDS-KS. Patients were treated biweekly with 10, 20, or 40 mg m-2 SL-DOX. Tumour response was assessed according to AIDS Clinical Trials Groups (ACTG) criteria before each cycle. Best response was determined for 238 patients and was achieved after a mean of 2.3 cycles (range 1-20). Fifteen patients (6.3%) had a complete response to SL-DOX, 177 (74.4%) had a partial response, 44 (18.5%) had stable disease and two (0.8%) had disease progression. SL-DOX was well tolerated: ten patients discontinued therapy because of adverse events, in four cases because of neutropenia. Grade 3 or 4 neutropenia occurred after 281 of 2023 cycles (13.9%) but involved 137 of 240 patients (57.1%) for whom data were available. SL-DOX has substantial activity in AIDS-KS. Best response is typically seen after fewer than three cycles of chemotherapy and in some cases may be prolonged. The most important adverse event is neutropenia, which occurs after a minority of cycles but which may occur in over half of all patients.
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PMID:Efficacy and safety of Stealth liposomal doxorubicin in AIDS-related Kaposi's sarcoma. The International SL-DOX Study Group. 861 37

Multiple interacting factors contribute to the haematological manifestations of HIV disease. The effects of HIV-1 infection influence all haemopoietic cell lineages resulting in a spectrum of haematological abnormalities. Even in the absence of other pathological processes, bone marrow morphology is invariably abnormal, and anaemia, neutropenia and thrombocytopenia are all common during the course of disease. Intercurrent opportunistic infections may cause bone marrow suppression or induce specific cytopenias. Therapies used to treat HIV and its complications are frequently implicated as the cause of haematological dysfunction, and many have significant myelotoxic side-effects. Insights into the molecular basis for many of these abnormalities have permitted a clearer understanding of the pathophysiology of HIV-1 infection. Recombinant human growth factors that may be used to treat isolated cytopenias or to ameliorate the myelotoxic effects of other essential therapies. Lymph opoietic growth factors and the use of gene modified cells provide future therapeutic strategies that may alter the course of HIV disease.
Baillieres Best Pract Res Clin Haematol 2000 Jun
PMID:Haematological aspects of HIV infection. 1094 22

Hairy-cell leukaemia (HCL) is a low grade B-cell lymphoproliferative process that presents either with lymphocytosis or neutropenia/monocytopenia. It is a disease predominantly of bone marrow and spleen, although it can also involve other organs and sites. Recent advances including multi-parameter flow cytometry and the development of antibodies with high specificity for HCL have permitted precise distinction of typical HCL from other lymphoproliferative diseases that can morphologically mimic the appearance of HCL. Although there is a commonly held belief that HCL is associated with a significant increase in second neoplasms, several recent studies have not supported this notion. The development of extremely effective therapy for HCL results in a high incidence of complete remission. However, a significant percentage of patients continue to harbour minimal residual disease that can be revealed with immunohistochemical and flow cytometric studies.
Best Pract Res Clin Haematol 2003 Mar
PMID:Pathology of hairy-cell leukaemia. 1267 Apr 62

Hairy-cell leukaemia is an indolent lymphoproliferative malignancy characterized by infiltration of the bone marrow, liver, spleen, and occasionally lymph nodes with a malignant B cell with hair-like cytoplasmic projections. This involvement leads to splenomegaly with secondary consumption of red cells, platelets and neutrophils as well as other complications of an enlarged spleen, including infarction-or-rarely rupture. The common haematological complications of anaemia, neutropenia and thrombocytopenia are due not only to the enlarged spleen but probably also to hairy cells in the bone marrow inducing cytokine-mediated suppression of haematopoiesis. Hepatic involvement, although frequent, only occasionally leads to liver dysfunction. Infections are a major cause of morbidity and mortality in patients with hairy-cell leukaemia, presumably owing to neutropenia and monocytopenia in these patients. The infections seen may be due to unusual pathogens, including Mycobacterium and Listeria. Autoimmune disease, including polyarthitis and vasculitis, occurs frequently and does not correlate with the severity of the disease. Other rare complications include bone involvement, meningitis and ascites. A wide range of secondary malignancies have been reported in patients with hairy-cell leukaemia, but it is still unclear whether the incidence is increased and whether they are related to the disease or treatment.
Best Pract Res Clin Haematol 2003 Mar
PMID:Clinical manifestations and infectious complications of hairy-cell leukaemia. 1267 Apr 63

Felty's syndrome (FS) comprises a triad of rheumatoid arthritis (RA), neutropenia and splenomegaly, occurring in less than 1% of RA patients. Clinically it is characterized by severe joint destruction contrasting with moderate or absent joint inflammation and severe extra-articular disease, including a high frequency of rheumatoid nodules, lymphadenopathy, hepatopathy, vasculitis, leg ulcers, skin pigmentation etc. Recurrent bacterial infections are mostly due to the severe, otherwise unexplained neutropenia. The cause of neutropenia lies in both decreased granulopoiesis and increased peripheral destruction of granulocytes. Recurrent infections may lead to increased mortality. Spontaneous remission of the syndrome also occurs. Over 95% of FS patients are positive for rheumatoid factor (RF), 47-100% are positive for antinuclear antibody (ANA), and 78% of patients have the HLA-DR4*0401 antigen. Some 30% of FS patients have large granular lymphocyte (LGL) expansion. LGL expansion associated with uncomplicated RA is immunogenetically and phenotypically very similar to but clinically different from FS. Neutropenia of FS can be effectively treated with disease-modifying anti-rheumatic drugs (DMARDs), the widest experience being with methotrexate (MTX). Results of treatment with granulocyte colony-stimulating factor (G-CSF) are encouraging, but there is no experience with other biological agents. Splenectomy results in immediate improvement of neutropenia in 80% of the patients, but the rate of infection decreases to a lesser degree.
Best Pract Res Clin Rheumatol 2004 Oct
PMID:Felty's syndrome. 1545 23

The 1-year survival for patients with metastatic non-small-cell lung cancer is only around 35%. We are evaluating the combination of irinotecan (Camptosar) and carboplatin (Paraplatin) in patients with stage IIIB and IV non-small-cell lung cancer. The first five patients received irinotecan, 250 mg/m2 over 90 minutes followed by carboplatin at an area under the concentration-time curve of 5 over 1 hour1 The dose of irinotecan was subsequently reduced to 200 mg/m2 in view of febrile neutropenia in one of five patients. Chemotherapy cycles are repeated every 21 days. Patients are reevaluated every two cycles. Of a planned 42 patients, 37 have been enrolled so far. Of the 37 enrolled patients, 25 received at least two cycles, 20 received at least four cycles, and 12 received all six planned cycles. Grade 4 neutropenia (absolute neutrophil count <500) occurred in 10 patients and 19 treatment cycles. Two of these patients also had grade 4 diarrhea. Thirty-six cycles (30%) were delayed for neutropenia, six of which occurred among the first five patients who received irinotecan at 250 mg/m2. Best response to therapy included 7 partial responses (23%), 11 stable disease (37%), with 12 patients having progressive disease (40%). The regimen of irinotecan and carboplatin administered once every 3 weeks is tolerable and convenient, with early evidence of activity. The main toxicity is hematologic. This study is ongoing and actively accruing patients.
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PMID:Irinotecan and carboplatin in metastatic or recurrent NSCLC: an update. 1568 28

Iron chelation is needed to prevent damage to the heart, liver and endocrine glands from iron overload in patients with refractory anaemias who receive regular blood transfusions. Desferrioxamine is still the first-line drug, but because of its expense in many countries, and lack of compliance because of difficulty with administration, there is a major need for an orally active (and cheaper) chelating drug. Seventeen years after the first clinical trials deferiprone, which is orally active, has emerged as suitable for patients for whom desferrioxamine is, for one reason or another, inadequate. Many patients are successfully chelated at a dose of deferiprone 75 mg/kg/day. Some patients may need higher doses (up to 100 mg/kg), or combination therapy of deferiprone every day and desferrioxamine on several days each week. Recent data suggest that deferiprone may be superior to desferrioxamine at protecting the heart from iron overload. The side-effects of deferiprone--agranulocytosis, neutropenia, gastrointestinal symptoms, arthropathy, transient changes in liver enzymes, and zinc deficiency--are now well recognized; they result in discontinuation of the drug in only 5-10% of patients. Deferiprone is now licensed in 43 countries for thalassaemia major patients for whom desferrioxamine is inadequate. If results of current trials confirm its superiority at reducing cardiac damage, it may well become the first-line drug for many patients.
Best Pract Res Clin Haematol 2005 Jun
PMID:Deferiprone therapy for transfusional iron overload. 1573 92

Neutropenic enterocolitis (NE) must be recognized in patients with fever, neutropenia, and abdominal pain. Classically, NE has been described in patients with hematologic malignancies treated with intensive chemotherapy. Current interest in NE has increased due to recent cases associated with newer, more intensive chemotherapy in solid tumors. This review discusses pathology, clinical presentation, and treatment of NE. Ultrasonography or CT scans are the best radiographic studies to confirm the diagnosis. Management options, including antimicrobial therapy, surgery, and supportive care, are discussed. Chemotherapy incorporating the taxane family of drugs (paclitaxel and docetaxel) associated with NE is also reviewed with observations regarding the earlier onset of the disease in the first weeks following chemotherapy. Even with currently recommended therapy, a high mortality rate, approximating 45%, can occur. Best outcomes for NE rely upon understanding of risks for the condition, prompt empiric therapy with broad-spectrum antimicrobial agents, systemic antifungal therapy, and meticulous attention to supportive care.
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PMID:Necrotizing enterocolitis in neutropenia and chemotherapy: a clinical update and old lessons relearned. 1683 46


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