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)

A phase Ib/II clinical study was undertaken to assess the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to attenuate neutropenia and associated morbidity caused by high-dose anticancer chemotherapy administered in the presence or absence of autologous bone marrow support. We treated 22 patients with various solid tumors and lymphoid neoplasias with a single daily subcutaneous dose of GM-CSF (250 micrograms/m2) 48 h after a second cycle of highly myelotoxic chemotherapy for a period of 10 days and compared intraindividually neutropenia-related clinical and laboratory variables with data obtained from the same patients having previously received a first neutropenia-inducing cycle of identical chemotherapy in the absence of GM-CSF. We show that GM-CSF is active in neutropenic patients by significantly increasing the neutrophil nadir, reducing the time of relevant neutropenia, and reducing the duration of the patient's hospital stay and necessity for parenteral antibiotics. No significant toxicity was encountered with subcutaneous GM-CSF treatment.
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PMID:Effect of granulocyte-macrophage colony-stimulating factor on neutropenia and related morbidity induced by myelotoxic chemotherapy. 218 61

The T cell chronic leukemias encompass a broad spectrum of diseases involving mature post-thymic T cells. With the development of highly specific marker studies, clear patterns of immunophenotypic and functional characteristics of the involved cells have emerged. These studies, along with the development of molecular probes for the T cell receptor gene loci, have helped to elucidate the pathogenetic basis for the highly variable clinical course which has been described for patients with these disorders. The T gamma lymphocytosis syndrome has been identified as a benign chronic illness which is nevertheless usually a monoclonal neoplastic proliferation of large granular lymphocytes. These patients represent a distinct clinical entity characterized by splenomegaly, neutropenia, and peripheral blood lymphocytosis. The cells of TGLS are large granular lymphocytes and display many of the immunophenotypic and functional characteristics of NK and K cells. These cells have been implicated pathogenetically in the associated cytopenias seen in the illness, but a clear link has not been established. Although the lymphoproliferative manifestations of the disease are usually easily controlled with low-dose alkylating agents, therapy of the neutropenia has been relatively unsuccessful. Separating these patients from the rest of the spectrum of the T cell chronic leukemias has provided insight into the other disorders as well. It has established that T-CLL and T-PLL are, in fact, extremely rare. T-CLL is similar to its B cell counterpart, except that patients have a higher incidence of skin infiltration. Available data suggest that the prognosis in T-CLL is actually less variable, and somewhat worse, than generally believed when those patients were viewed in conjunction with the patients with the more benign TGLS. T-PLL is an extremely aggressive disease characterized by massive splenomegaly, lymphadenopathy, and skin infiltration. It is refractory to most forms of therapy. These illnesses are again phenotypically distinct from the retrovirus-associated ATLL. Most of the early cases of T-CLL reported from Japan were probably ATLL; this disease is characterized by pronounced splenomegaly, hepatomegaly, lymphadenopathy, and skin infiltration. It has an extremely aggressive natural history, and survival is usually less than 1 year from diagnosis. The rapid development of sophisticated immunologic and molecular techniques for analyzing T cell proliferations has allowed highly specific distinctions to be made among the cells of origin of the different T cell chronic leukemias. It is hoped that increased understanding of the immunologic and functional characteristics of these diverse T lymphoid populations will provide further insights which will have an impact on directed therapeutic interventions in the future.
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PMID:T gamma lymphocytosis and T cell chronic leukemias. 218 3

Fostriecin, a novel anticancer antibiotic produced by Streptomyces pulveraecus, is believed to act via inhibition of topoisomerase II. Single-dose intravenous administration to rats at dose levels of 8.8 to 48 mg/kg resulted in lethality at dose levels of 35 mg/kg and higher. Major toxic effects were observed primarily at 17.5 mg/kg and higher, were reversible, and consisted of bone marrow hypocellularity, leukopenia, neutropenia, thrombocytopenia, and diffuse necrosis of various lymphoid tissues. The kidney was also identified as a target organ. Renal effects were observed primarily at 20 mg/kg, were reversible, and included increases in serum BUN, creatinine, and 24-hr glucose excretion. Twenty-four-hour excretion of Na+, K+ and urine osmolality were decreased postdosing at 10 and 20 mg/kg. Renal lesions, observed primarily at 20 mg/kg, consisted of vacuolization and necrosis of proximal and distal tubular epithelium at the corticomedullary junction extending into the medulla. Repeated daily intravenous administration of fostriecin for 5 days to rats at dose levels of 2.5 to 26.5 mg/kg resulted in death at 10 mg/kg and above and similar hematologic, bone marrow, lymphoid tissue, and renal changes as observed in the single-dose study. Hematological, bone marrow, lymphoid, and renal changes observed in rats were consistent with the cytotoxic mechanism of action of the compound.
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PMID:Preclinical toxicological evaluation of fostriecin, a novel anticancer antibiotic, in rats. 222 54

Eight patients with Hyper-IgM syndrome were subjected to clinical and immunological evaluation. There were seven males and one female. All the patients had recurrent pyogenic infections; one had lymphoid hyperplasia with centrally necrotic granulomas, and one had gingivitis with neutropenia. Isohemagglutinin titers were either high or normal in all the patients and five had group 0 blood. The percentage of IgM-bearing cells were normal in five patients. The percentage of T cells were normal in all the patients, helper T cells were decreased in two patients, and suppressor T cells were increased in four patients. These results suggest that at least in some patients, the imbalances of T cell subsets may play a role in the pathogenesis of the disease rather than it being attributed to an intrinsic B cell defect.
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PMID:Clinical and immunological aspects of hyper-IgM syndrome. 228 14

Two cases of Kikuchi's histiocytic necrotizing lymphadenitis diagnosed by fine needle aspiration (FNA) of enlarged lymph nodes are reported. The FNA smears contained randomly activated lymphoid cells, necrotic debris, karyorrhectic cells and prominent histiocytes, suggesting the presence of reactive lymph nodes. The true nature of the lesions was evident from the examination of cell block sections prepared from tissue fragments in the aspirates, which preserved the architectural relationships of the different cell types. The same patterns were found in retrospectively and subsequently examined excised lymph nodes from these cases. The differential diagnosis of this entity, which may simulate a malignant lymphoma because of the presence of large numbers of activated lymphoid cells, is discussed and the value of preparing FNA cell blocks is emphasized. Though this rare benign disease may be suspected clinically in the more typical cases, such as young women with cervical lymphadenopathy, fever, neutropenia and otherwise excellent condition, the diagnosis cannot be made without a lymph node biopsy, which FNA may be able to provide in some instances.
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PMID:Kikuchi's histiocytic necrotizing lymphadenitis. Diagnosis by fine needle aspiration. 234 86

In an attempt to stimulate granulopoiesis, we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to 11 patients with lymphoproliferative disorders. Ten patients had neutropenia, six of whom had severe neutropenia (less than 500 neutrophils), including two with agranulocytosis. GM-CSF (60-250 micrograms/m2/day) was administered by continuous intravenous infusion daily for 14 days at 2-week intervals. Significant increases in white blood cell counts (1.3-to 11.7-fold) and neutrophils (1.7- to more than 29-fold) were seen in 10 of 11 patients, including one patient with agranulocytosis. Eosinophils (3.9- to greater than 65-fold) and monocytes (1.3- to 5-fold) increased as well. In contrast, no significant increases were seen in total lymphocytes or in different phenotypic subsets of lymphocytes during treatment. The overall proportion of myeloid and lymphoid elements in bone marrow remained stable. These results indicate that GM-CSF is effective in stimulating myelopoiesis in neutropenic states associated with lymphoproliferative disorders. Further studies will be necessary to determine whether the correction of neutropenia ultimately translates into clinical benefit.
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PMID:Stimulation of myelopoiesis in chronic lymphocytic leukemia and in other lymphoproliferative disorders by recombinant human granulocyte-macrophage colony-stimulating factor. 240 49

The genes for a number of growth factors that stimulate human hematopoietic and lymphoid cells in vitro have recently been cloned and recombinant molecules provided for clinical trials. For three of these (erythropoietin, G-CSF, and GM-CSF), phase I and II studies have been completed and promising results have been obtained. Of particular relevance to the field of bone marrow transplantation (BMT) has been the finding that G-CSF and GM-CSF could shorten the period of neutropenia in patients treated with chemotherapy, including regimens requiring BMT support. Doses of up to 240 micrograms/m2 of GM-CSF have been well tolerated and have increased the peripheral blood neutrophil count in a dose-dependent manner. At higher doses, eosinophils and monocytes were also increased. A continuous infusion over at least 2 h was found to be superior to bolus administration in terms of both efficacy and reduced side effects. These have usually been mild, but bone pain, headache, fatigue and elevated temperature have been encountered. The rise in neutrophil numbers shortly after initiating treatment with GM-CSF is probably due to neutrophil demargination. After a few days increased bone marrow cellularity has also been noted. In addition to these effects on cell numbers, enhancement of granulocyte and monocyte functions has been documented. However, a major concern with the use of G-CSF and GM-CSF in cancer patients, particularly those with hematopoietic malignancies, is the potential of these molecules to stimulate malignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony stimulating factors. 245 88

Feline immunodeficiency virus (FIV; formerly, feline T-lymphotropic lentivirus) is a typical lentivirus resembling human and simian immunodeficiency viruses in morphologic features, protein structure, and reverse transcriptase enzyme. It is antigenically dissimilar, however. The virus is tropic for primary and permanent feline T-lymphoblastoid cells and Crandell feline kidney cells. The virus did not grow in other permanent feline non-lymphoblastoid cells that were tested, or in lymphoid and non-lymphoid cells from man, dogs, mice, and sheep. During short-term inoculation studies in cats, the feline immunodeficiency-like syndrome found in nature was not experimentally induced, but a distinct primary phase of infection was observed. Fever and neutropenia were observed 4 to 5 weeks after inoculation; fever lasted several days, and neutropenia persisted from 1 to 9 weeks. Generalized lymphadenopathy that persisted for 2 to 9 months appeared at the same time. Antibodies to FIV appeared 2 weeks after inoculation and then plateaued. Virus was reisolated from the blood of all infected cats within 4 to 5 weeks after inoculation and persisted indefinitely in the face of humoral antibody response. Virus was recovered from blood, plasma, CSF and saliva, but not from colostrum or milk. Contact transmission was achieved slowly in one colony of naturally infected cats, but not between experimentally infected and susceptible specific-pathogen-free cats kept together for periods as long as 4 to 14 months. The infection was transmitted readily, however, by parenteral inoculation with blood, plasma, or infective cell culture fluids. In utero and lactogenic transmission were not observed in kittens born to naturally or experimentally infected queens. Lymphadenopathy observed during the initial stage of FIV infection was ascribed to lymphoid hyperplasia and follicular dysplasia. A myeloproliferative disorder was observed in 1 cat with experimentally induced infection.
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PMID:Pathogenesis of experimentally induced feline immunodeficiency virus infection in cats. 245 96

The myeloid growth factors are a promising new class of therapeutic agents with the potential for broad clinical application. Four recombinant myeloid growth factors, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin (IL)-3 are available for clinical trials. GM-CSF has been studied in leukopenia related to acquired immunodeficiency syndrome (AIDS), aplastic anemia, and myelodysplasia, as well as in patients receiving chemotherapy and those undergoing autologous bone marrow transplantation. In these trials, GM-CSF was demonstrated to increase the number of neutrophils, eosinophils, and monocytes with corresponding bone marrow changes. Toxicity is dose-related, and maximum tolerated dosages are in the range of 16 to 32 micrograms/kg/day. The effects of daily subcutaneous administration of GM-CSF appear to be similar to those of intravenous (IV) administration. G-CSF, studied mainly in the treatment of neutropenia following cytotoxic chemotherapy, was found to decrease the duration of severe neutropenia as well as the risk of infections. G-CSF causes prominent increases in neutrophil levels without affecting eosinophils or monocytes. Associated toxicity is minimal, and subcutaneous administration is efficacious. Preliminary evidence suggests that G-CSF may also have a therapeutic role in indolent lymphoid neoplasms complicated by neutropenia. Administration of natural M-CSF to patients receiving chemotherapy and those with chronic childhood neutropenia has shown modest neutrophil increases. Preclinical data on IL-3 suggest that this agent increases neutrophils, eosinophils, basophils, reticulocytes, and possibly platelets.
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PMID:Clinical applications of the myeloid growth factors. 247 Dec 74

Clinical trials of recombinant biologic agents have resulted in new treatment options for hematologic, oncologic, and cardiologic disorders. These agents include the interferons, recombinant human erythropoietin (r-HuEPO), colony-stimulating factors (CSFs), interleukins (ILs), and tissue plasminogen activator (t-PA). Interferon alfa has proven efficacious in treating certain hematologic malignancies and solid tumors and has recently been indicated for acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Treatment with r-HuEPO has relieved the chronic anemia of hemodialysis patients. Recombinant human granulocyte CSF (G-CSF) or human granulocyte macrophage CSF (GM-CSF) has been used to treat patients after autologous bone marrow transplantation for lymphoid or solid malignancies, resulting in increased production of granulocytes and platelets. G-CSF and GM-CSF have been used to treat aplastic anemia, myelodysplastic syndromes, chemotherapy-induced neutropenia, and neutropenia associated with AIDS. In patients with evolving myocardial infarction, the recombinant agent t-PA has proved more efficacious than streptokinase in terms of average coronary artery patency rates and survival rates in patients with evolving myocardial infarction. While these agents all offer promising therapeutic advances, the expenses associated with developing and testing biotherapeutic substances have resulted in high treatment costs. Since in many instances investigational therapy is the best treatment option available, physicians, patients, the pharmaceutical industry, the government, and insurance carriers must work together to ensure that these therapies are financially available to those in need.
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PMID:New directions in hematologic biotherapy. 247 3


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