Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective, controlled, randomized study to evaluate the efficacy of filtration-leukapheresis granulocytes in granulocytopenic, febrile patients with leukemia, 19 patients received antibiotics alone, and 12 received antibiotics plus daily granulocyte transfusions from ABO-matched donors. In skin-chamber studies the granulocytes appeared at sites of inflammation for at least six hours after transfusion. Infected subjects survived longer if they received granulocytes. Differences between control and transfused patients were greatest in patients with persistent bone-marrow failure, the 21-day survival being 20 per cent in controls, and 75 per cent in transfused patients. Granulocytes appeared to have no effect on the outcome of febrile episodes in which infection was not documented, the 21-day survival being 79 per cent for controls and 88 per cent for transfused patients. The transfusion of granulocytes thus appears to offer a survival advantage to infected, persistently granulocytopenic patients.
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PMID:A randomized clinical trial of granulocyte transfusions for infection in acute leukemia. 32 Apr 77

An antiserum raised against myelomonocytic and monocytic leukaemia cells has been used to define a cell surface antigen shared by normal and leukaemic cells of the granulocyte and monocyte cell lines. The quantitative expression of this antigen was investigated using the Fluorescence Activated Cell Sorter and was shown to correlate with the degree of morphological maturation.
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PMID:Maturation linked expression of a myeloid cell surface antigen. 34 27

The paper reviews methods of studying cell kinetics in man, cell population kinetics of human tumors and bone marrow, drug interactions and the cell cycle, and possible applications to chemotherapy. The conclusions drawn are: (1) Cell cycle time and S-phase duration for proliferating granulocyte precursors in human bone marrow are poorly defined but are probably shorter than median values for most human tumors, including leukemia. (2) Most drugs have greater toxicity for cycling cells and some variation in toxicity at different phases of the cell cycle. There is a special need for chemotherapy directed at slowly proliferating and hypoxic tumor cells. (3) Pretreatment indices of tumor cell kinetics are of little value in choosing drugs or in predicting response. (4) Experiments in animals have demonstrated that therapeutic index may depend on schedule. Knowledge of cell kinetics in animals rarely allows prediction of the optimal schedule and is unlikely to do so in man. Optimal schedules in mice are not directly relevant to man. (5) Measurement of tumor labeling index or DNA histogram by flow microfluorimetry to detect cell synchrony is of little benefit in scheduling if concurrent changes in bone marrow are ignored; these methods are invalid at short intervals after treatment because surviving clonogenic cells are indistinguishable from a larger number of drug-damaged cells prior to their lysis. (6) The major factor determining the outcome of chemotherapy is the availability of drugs with activity for the tumor and acceptable host toxicity. Claims that complex schedules using several drugs are effective because of synchrony or kinetic differences of tumor and normal tissue are at present unsubstantiated.
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PMID:Cell kinetics and chemotherapy: a critical review. 35 75

The production of white blood cells is mediated by cellular communication. Proliferation and differentiation of granulocytic and monocytic progenitor and immature cells have been studied in detail and are regulated by stimulatory and inhibitory molecules produced and released from the progeny of the progenitor cells. The resultant interactions between cells and cell-derived molecules suggest operable positive and negative feed-back mechanisms during normal hematopoiesis, and what one sees in the end is the net result of these interactions. The complexities of cellular regulation are partially unravelled by physical separation of the different populations and biochemical analysis of the regulatory molecules. Subpopulations of granulocyte-monocyte progenitors (CFU-c) exist and evidence suggests that they vary in responsiveness to different molecules. Stimulatory molecules are themselves chemically and physically heterogenous and, until recently, believed to have similar biological actions, but this concept must be re-evaluated. Different molecules may activate different subsets of progenitor cells, and there is now a role for substances which enhance the stimulatory interactions. Many studies on normal and leukemic cell responsiveness to stimulation must be re-examined in light of this recent information. Several inhibitory substances operate during normal hematopoiesis. Mature granulocytes, progeny of CFU-c, appear to elaborate at least two inhibitory activities. One activity influences immature, recognizable granulocytes and the other indirectly reduces progenitor cell proliferation by decreasing the production and release of molecules which stimulate CFU-c. In addition, mononuclear phagocytes produce and release E-type prostaglandins in direct response to elevated levels of the stimulatory molecules and E-type prostaglandins counteract increased stimulatory levels by decreasing the sensitivity of CFU-c to stimulators. Much of our present level of sophistication derives from in vitro experimentation and it is apparent that we are only beginning to understand these inter-relationships and their relevance to the in vivo situation. However, these in vitro studies have shed light on the interactions occurring during leukemia. Leukemic cells retain the capacity to respond to normal regulators and must therefore be considered dependent rather than autonomous neoplasms. Abnormalities do exist in leukemic cell interactions: the progenitor cells themselves may be defective and leukemic cells may respond to molecules which normal cells do not. The degree of sensitivity to stimulators and inhibitors will have to be carefully investigated to determine if and what differences may exist between normal and leukemic cells. Normal mature granulocyte derived inhibitory activity is quantitatively deficient in leukemic cells but another inhibitory activity which appears to be specifically present in cells from patients with leukemia and some cases of myelodysplasia is present...
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PMID:Communication between white cells and the abnormalities of this in leukemia. 36 38

High titer, monospecific antibodies to human granulocyte myeloperoxidase, cathepsin G, elastase, lysozyme, and lactoferrin were conjugated with fluorescein and rhodamine and used for immunofluorescent staining of mature neutrophils obtained from 25 patients with acute and chronic leukemia. In 11 (44%) of the patients, two populations of mature neutrophils were detected. The abnormal cells were identified by complete deficiency of one or more markers and constituted 10%-100% of the total number of neutrophils. This immunocytochemical approach may permit recognition of mature cells derived from leukemic clones, and serial determinations of the ratio of normal to abnormal cells may be useful in the management of patients with leukemia.
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PMID:Immunocytochemical identification of abnormal polymorphonuclear neutrophils in patients with leukemia. 40 Aug 91

The most important factors of infection in leukemic patients and immunodepressive effect of chemotherapy are evaluated. The microorganisms causing infections most frequently are considered. The associations of antibiotics for therapy of severe infections are reported. The employement of granulocyte transfusion, in patients with severe neutropenia and infections antibiotico-resistents, is also considered. Dealing with patients liable of infections the possibility of infection prevention and therapy in protected environment is faced. 12 patients affected by acute nonlymphocitic leukemia were treated with cytostatic drugs to induce remission in laminar air flow room. The number of infections is significantly decreased in comparison with of patients treated in open ward. In protected environment it is possible to treat patients with the maximal dose of antiblastic drugs without interruption obtaining higher number of complete remission.
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PMID:[The problem of infections in acute leukemias: origin, therapy and prevention by protective isolation]. 41 88

Thirty-six febrile neutropenic episodes were treated by granulocyte transfusions in 33 children. Septicemia and mucous membrane ulcerations were most commonly associated with the fever. Infection cleared in 81% of the episodes, eight per cent ended in death from bacterial infections, 11% from nonbacterial infections or hemorrhage. The median number of polymorphonuclear leukocytes given was 1.1 X 10(10)/m2/transfusion. Two to twenty-eight (median 8.5) transfusions were given over 3--34 days (median 10.5). The source of cells (parental or random) and the method of collection did not seem to affect the outcome. None of the 23 patients whose marrow recovered during the transfusions died of bacterial infections. Infection cleared even without marrow recovery in 62% of the patients, but then only 25% lived for more than two months after clearing of sepsis. In a subgroup of patients with nonlymphoblastic leukemia on the same chemotherapy and antibiotic treatment protocol, 8/11 (73%) survived bacteremia when white cell support was available; only 2/11 (18%) of a historical control group survived when such support was not available. Granulocyte support appears to be a valuable tool in helping neutropenic patients overcome their infections or, at the very least, helping them survive long enough for normal marrow recovery to occur.
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PMID:Granulocyte transfusions in infected neutropenic children with malignancies. 44 Feb 6

The effect of the naturally occuring amino acids upon melphalan (L-phenylalanine mustard, L-PAM) toxicity to a host sensitive tissue, the granulocyte and macrophage precursor cells of murine bone marrow (CFU-C), was investigated. At physiological concentrations the L isomers of leucine and glutamine were found to be the most effective of the naturally occurring amino acids in reducing drug toxicity. Tyrosine, phenylalanine and methionine also protected murine CFU-C from melphalan toxicity although the amount of protection provided by these amino acids at physiological concentrations was less than that provided by leucine and glutamine. Little difference was observed in the pattern of amino acid protection of murine CFU-C and murine L1210 leukemia cells. Murine CFU-C however were more sensitive to melphalan both in the absence and presence of amino acids.
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PMID:Amino acid conferred protection against melphalan: comparison of amino acids which reduce melphalan toxicity to murine bone marrow precursor cells (CFU-C) and murine L1210 leukemia cells. 44 10

Thirteen leukemic patients with disease refractory to conventional chemotherapy were treated with 1.0 to 7.5 g/m2 of Cytosine Arabinoside (Ara-C) over 29 drug cycles. Drug infusions were spaced at 12-hour intervals; a maximum of four doses was administered over 36 hours. After single dose tolerance had been established, three or four dose cycles were given at 2- to 30-day intervals. There were three partial remissions (PR) and one complete remission (CR) in a treatment group of four patients with AML, five with ALL, two with lymphoma converted to leukemic phase, one CML in blast crisis, and one promyelocytic leukemia. Five of the patients were septic and considered terminally ill at the time of treatment. All other patients had evidence of drug responsiveness. The nadir of the white count occurred from 3 to 12 days after treatment, with subsequent recovery of the peripheral granulocyte count between days 12 and 28. Toxicity included nausea and vomiting (GI symptoms) in twelve patients, central nervous system (CNS) disturbances in eight patients, one episode of inappropriate antidiuretic hormone syndromes (SIADH), one of hyperuricemia, and fever in eleven patients. There was no evidence of hepatic or renal dysfunction. These high doses of Ara-C appear useful for treatment of patients with refractory leukemia. Hospitalization is brief and toxicity acceptable.
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PMID:High dose cytosine arabinoside (HDARAC) in refractory acute leukemia. 49 9

Drug like aspirin, indomethacin, phenylbutazone, chloroquine and quinine have been reported to induce agranulocytosis, aplastic anaemia and leukemia. These drugs are also known to interfere with the prostaglandin system at one point or another. Since prostaglandins are known to be involved in the maturation and differentiation of macrophage-granulocyte progenitor cells, in erythropoietin mediated erythropoiesis and in the functional capabilities of leukocytes, it is proposed here that these haematological abnormalities by these drugs could be due to their affect on the prostaglandin system.
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PMID:Prostaglandins and drug induced agranulocytosis, aplastic anaemia and leukemia. 55 Jan 46


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