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)

Difluoromethylornithine (DFMO), a non-competitive inhibitor of ornithine decarboxylase (ODC), the rate limiting enzyme of the polyamine synthetic pathway was evaluated in a Phase I trial. Intravenous DFMO was given to twenty patients with refractory leukemia by continuous infusion in doses from 5.5 to 64 g/m2. Toxicity clearly attributable to the drug was not severe and other than nausea and vomiting did not increase with dose. The previously reported ototoxicity which occurred with the oral form appeared to be less frequent. Loss of hearing which improved when the drug was stopped was seen in four patients, three of whom were simultaneously receiving aminoglycosides. Anorexia occurred in some patients at all doses. Vomiting, necessitating dosage reduction, was a significant problem at the highest dose administered. No patient achieved a remission but there was stabilization or decrease in circulating blast cells in several patients. This growth inhibition did not appear to be dosage related.
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PMID:Phase I evaluation of intravenous difluoromethylornithine--a polyamine inhibitor. 393 6

A transient cerebral disturbance characterized by somnolence of varying degree is described in children after cranial irradiation given as part of central nervous system (C.N.S.) prophylaxis for acute lymphoblastic leukaemia in remission.Out of 28 such children receiving cranial irradiation as part of the Medical Research Council protocol for C.N.S. prophylaxis 11 (39%) developed pronounced symptoms of somnolence, anorexia, and lethargy some six weeks after the completion of cranial irradiation, and a further 11 (39%) developed these features in mild form. In all cases the symptoms were transient, no focal neurological abnormality was detected, and all children made a spontaneous and complete recovery. E.E.G. studies on five somnolent children showed similar abnormal activity of diffuse and patchy distribution over both hemispheres. Indirect evidence is presented to support the concept that this syndrome represents a transient radiation encephalopathy, analogous to acute transient radiation myelopathy, caused by temporary disturbance of myelin synthesis.
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PMID:Somnolence after prophylactic cranial irradiation in children with acute lymphoblastic leukaemia. 451 11

Four new cases of acute myelofibrosis are reported, and 63 cases reported in the literature are reviewed. The typical features of this disease include a rapidly progressive clinical course; nonspecific symptoms such as weight loss, anorexia, fatigue and weakness; the absence of organomegaly; pancytopenia; circulating blast cells; and mild abnormalities in the red blood cell morphology. The bone marrow aspirates are usually "dry." The bone marrow biopsies are essential for the diagnosis and show four consistent features: hypercellularity, reticulin fibrosis, proliferation of blast cells and bizarre, atypical megakaryocytes. In 16 cases, the blast cells in peripheral blood and bone marrow, which are unclassifiable by conventional morphology, could be identified as megakaryoblasts by ultrastructural and immunocytochemical techniques. It is concluded that acute myelofibrosis is a definite clinicopathologic entity, which may be related to acute megakaryoblastic leukemia.
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PMID:Acute myelofibrosis. A report of four cases and review of the literature. 637 42

Twenty-three cases of hematological malignancies (18 plasma cell neoplasm, 2 leukemia and 2 malignant lymphoma) were treated with recombinant human leukocyte interferon (rIFN-alpha A). Among plasma cell neoplasms, excellent and good responses were obtained in 1 case of IgG myeloma and 1 case of Bence-Jones myeloma respectively and fair response was obtained in 5 other cases. Response rats was 11.4%, or 38.9% if fair response was included. Partial remission was obtained in 1 case of chronic lymphocytic leukemia. In one of 2 cases of acute lymphoblastic leukemia, marked reduction of peripheral leukemia cells was noted. Side effects included fever (65%), malaise (20%), nausea-anorexia (43%), leukopenia (52%) and thrombocytopenia (52%). However, all were not serious and disappeared quickly after discontinuation of rIFN-alpha A.
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PMID:[Treatment of hematological malignancies with recombinant leukocyte A interferon (rIFN-alpha A)]. 659 73

Two metabolites of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) were found in the plasma and urine, and a hydrolytic product, arabinosylcytosine (ara-C) and its deaminated product, arabinosyluraci (ara-U), were found in a preclinical study using monkeys. Of a given dose, 96% was found as ara-U and 3% as ara-C in urine in 24 h. The plasma disappearance curve of BH-AC is biphasic; the half-life of the initial phase is 40 min and that of the second phase is 120 min. At 8 h the BH-AC level is 21.9 micrograms/ml and falls exponentially to 3.6 micrograms/ml by 12 h. Ara-C was detected at the levels of 0.4-0.6 microgram/ml for 4 h. Comparative data of pharmacokinetic parameters among BH-AC, ara-C, and O2,2'-cyclocytidine showed that BH-AC had the longest plasma half-life, the smallest elimination-rate constant and the smallest excretion-rate constant. The plasma-clearance study of BH-AC in 13 patients showed essentially a pattern similar to that in monkeys; the plasma t 1/2 of 60 min in the first phase and of 180 min in the second. The BH-AC level at 2 h is 15.4 micrograms/ml, and 1.8 microgram/ml at 8 h. Initial phase I study of BH-AC was evaluated in 14 patients with leukemia and other malignancies. The starting dose was 1.5 mg/kg given as a single IV infusion for 3. The doses were when escalated up to 5.0 mg/kg. No side effects were noted with a single dose schedule. Daily consecutive infusions of 2.0 mg/kg-6.0 mg/kg for 4-21 days resulted in two patients having nausea, two anorexia, and one developing skin eruptions. Significant hematologic effects were noted with the daily infusion. One patient with acute myeloblastic leukemia achieved complete remission with 5.0 mg/kg BH-AC given daily for 21 days. It pharmacologic features, minimal toxicity, and the capability of inducing complete remission in acute leukemia indicate that BH-AC undoubtedly deserves further prospective clinical trials.
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PMID:Pharmacologic and clinical studies of N4-behenoyl-1-beta-D-arabinofuranosylcytosine. 676 63

A 9-year-old boy presented with increasing fatigue, anorexia, weight loss, fever, and absolute eosinophilia (48,000/microL). Pulmonary infiltrates occurred 3 months later. A murmur of mitral regurgitation was heard 5 months after onset of illness, and heart failure soon followed. Despite corticosteroid therapy the eosinophilia persisted intermittently until 1 month before death. The patient died within 9 months of the onset of illness. At necropsy there was cardiomegaly with subendocardial fibrosis in the right and left ventricles. Thrombi were present in the left ventricular apex and behind the posterior mitral leaflet. The findings in 12 previously reported pediatric cases are reviewed. The etiopathogenesis of the hypereosinophilic syndrome is discussed: half of the cases in children are associated with leukemia.
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PMID:Cardiomyopathy in a child with hypereosinophilic syndrome. 715 51

A phase I study of human lymphoblastoid interferon (IFN-alpha) was undertaken in patients with acute leukaemia and other malignancies. The pharmacokinetics of intravenous IFN-alpha were also investigated. IFN-alpha was administered to two patients by intravenous (IV) bolus injection at a dose of 5 X 10(6) U/m2; and to a further 37 patients (40 cycles) by continuous intravenous infusion (IVI) for 5, 7, or 10 days at doses ranging from 5 to 200 X 10(6) U/m2/day. Pyrexia, general malaise, anorexia, and rigors were observed at all dose levels; three patients became hypotensive. Myelosuppression occurred in all patients, including seven without bone marrow infiltration. Transient rises in alkaline phosphatase and transaminases (SGOT) were observed in patients receiving daily doses greater than 30 X 10(6) U/m2. Dose-limiting central nervous system toxicity, hyperkalaemia, and hypocalcaemia were encountered at 200 X 10(6) U/m2. In six patients with acute leukaemia there was a fall in the number of circulating leukaemic blasts and in one patient with acute myelogenous leukaemia (AML) the degree of bone marrow infiltration decreased from 99% to less than 5% with cellularity returning to normal. Serum levels of IFN above 1,000 U/ml were achieved with daily doses above 30 X 10(6) U/m2 given by IVI. The maximum safely tolerated daily dose, 100 X 10(6) U/m2 administered for 7 days, is appreciably higher than that used in most previous studies, although even at this level considerable toxicity may be encountered.
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PMID:A phase I study of human lymphoblastoid interferon administered by continuous intravenous infusion. 717 12

The antitumor effect of thymidine has been demonstrated in patients with leukemia and lymphoma. This report summarizes the treatment of three patients with mycosis fungoides, a chronic T-cell lymphoma. Four courses of thymidine (75 g/m2/day) were administered by continuous infusion for 4-7 days. Steady-state serum thymidine levels were in the range of 1-3 mM. Associated toxicities were minimal and consisted of milk headache and anorexia. Myelosuppression was manifested by transient declines in the peripheral leukocyte count. One patient had extensive clearing of diffuse erythematous plaques on the trunk and extremities that persisted for over one month. A second patient had partial clearing of plaques that persisted for two weeks following therapy and a third patient had a minimal response with 25% reduction in lymphadenopathy and noduloulcerative lesions. These responses indicate the effectiveness of thymidine as a single agent in the treatment of mycosis fungoides.
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PMID:Effect of high-dose thymidine infusions in patients with mycosis fungoides. 728 56

The camptothecin analogues topotecan and irinotecan (CPT-11) are active anticancer drugs. This article reviews the accumulated results of clinical and laboratory studies performed with these agents at The Johns Hopkins Oncology Center. In a phase I clinical and pharmacology trial of topotecan given as a 30-min infusion daily for 5 days every 3 weeks, profound neutropenia precluded dose escalation above 1.5-2.0 mg/m2 per day, the maximum tolerated dose (MTD). The daily x5 schedule has been developed further with dose escalation using granulocyte-colony-stimulating factor support in patients who have kidney or liver dysfunction and given in combination with cisplatin. In addition, a phase I trial of topotecan given as a 5-day continuous intravenous infusion to patients with refractory leukemia has had promising antileukemic responses. A separate series of in vitro studies indicates that a modest degree of resistance to the cytotoxicity of topotecan can be mediated by P-glycoprotein. A phase I and pharmacology study of irinotecan given as a 90-min infusion every 3 weeks has defined an MTD of 240 mg/m2, with dose escalation being limited by several toxicities. These included an acute treatment-related syndrome of flushing, warmth, nausea, vomiting, and diarrhea; a subacute combination of nausea, diarrhea, anorexia, and weight loss; and/or neutropenia. Antitumor activity has been observed with topotecan and irinotecan in patients with a variety of solid tumors and refractory leukemia in our studies, which supports the widespread enthusiasm for this group of compounds.
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PMID:Camptothecin analogues: studies from the Johns Hopkins Oncology Center. 752 Aug 44

Five acute leukaemia or highly malignant lymphoma patients at a hospital in southern Sweden were interviewed about their daily living problems, their coping strategies and their opinions about the nursing care they received during the active phase of their treatment. In addition the EORTC QLQ-C30, the Global Life Quality and the Sense of Coherence scales were administered. The data were analysed from a hermeneutic phenomenological perspective and interpreted to indicate that the patients sensed a threat to their lives, loss of control, and having to live with uncertainty stemming from the disease and the treatment. They had problems with fatigue, diarrhoea, nausea and vomiting, loss of appetite, sore mouth and high temperature. However, they seemed to minimize the importance of these problems and instead focused on gaining control of the situation, developing their knowledge of the disease and relying on the support of their family. Contradictions appeared in their statements about the quality of care, the information given was said to be good but difficult to understand; although the quality of the nursing care was judged to be high it had to be asked for. That is, help was received on request. The patients' perspective of the family and the nurses should be studied in further research in order to fully understand the patients' coping strategies and how nursing care can support them.
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PMID:Acute leukaemia and malignant lymphoma patients' experiences of disease, treatment and nursing care during the active treatment phase: an explorative study. 755 23


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