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)

A pilot study was carried out among 21 patients with advanced solid tumors to establish appropriate dose levels of PALA and 5-FU given on a 5-day schedule to produce definite but tolerable clinical toxicity. While dermatitis, diarrhea, leukopenia, and thrombocytopenia were observed, stomatitis was the dose-limiting side effect. The recommended initial dose levels for further clinical trials are 625 mg/m2 of PALA daily x 5 and 250-300 mg/m2 of 5-FU daily x 5, with courses repeated at 4-week intervals. Studies were also conducted to establish the time course of anticipated increased incorporation of 5-FU into cellular RNA following treatment with PALA. In murine P388 leukemia, PALA increased tritiated 5-FU incorporation by as much as 70%, the effect being maximal within 1 hour and maintained up to 25 hours. It was not possible to demonstrate increased tritiated 5-FU uptake into normal human leukocyte RNA from patients receiving combination chemotherapy with PALA and 5-FU, perhaps because of low rates of RNA synthesis.
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PMID:Pilot study of PALA and 5-FU in patients with advanced cancer. 705 70

Four patients with acute nonlymphoblastic leukemia and one malignant teratoma refractory to conventional chemotherapy were treated with high doses of cytosine arabinoside (HD ARA-C). They received up to 12 cycles of 1.8 to 3 g/m2 every 12 hours applied by 2-hour infusions. A total of 55 HD ARA-C infusions was performed. All leukemic patients responded. A complete clearance of blasts from the bone marrow was observed in two patients following 8-12 cycles of 3 g/m2. However, relapses occurred after three and seven weeks, in one case with resistance to HD ARA-C. The patient with malignant teratoma did not respond. No severe toxicity emerged even after repeated applications. Adverse reactions included moderate nausea and vomiting (4 patients), diarrhea (2 patients), hepatic dysfunction (1 patient), bone pain (1 patient), blurred vision (1 patient), conjunctivitis (1 patient), and exanthema with partial epidermiolysis (1 patient). Granulocytopenia occurring between 3-8 days after having started the therapy, subsided within 4-25 days. Plasma levels of ARA-C and the metabolite uracil arabinoside (ARA-U) were monitored. At steady state plasma concentrations of ARA-C were 32-97 microM (8-24 micrograms/ml). ARA-C disappeared from the plasma mono- or biphasic with a terminal half-life (t50%) of 7.8-12.6 minutes. The total clearance (Cl) of ARA-C varied between 1.7 and 2.9 liters/kg . h, and the distribution volume (Vss) between 0.44 and 0.86 liters/kg. Cerebrospinal fluid (CSF) levels of ARA-C reached 10-15% of steady state concentrations in plasma.
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PMID:Clinical results and pharmacokinetics of high-dose cytosine arabinoside (HD ARA-C). 710 69

The state of child health in Singapore from 1914 to the present is discussed. In 1914 there were 225 reported cases of tetanus neonatorum out of 7420 births and 340 deaths from gastroenteritis with an infant mortality rate (IMR) of 292.9/1000 live births. In 1936 the IMR was 167.74 and in 1962 it was still high at 31.2. Causes of death included tetanus neonatorum, gastroenteritis, tuberculosis, and poliomyelitis. Diphtheria immunization had lowered the rate of mortality from this disease. The 1st priority in improving infant health after 1962 was lowering the IMR, especially by treating the newborn. The 2nd priority was infections. Oral Sabin was introduced against polio and programs for tetanus, whooping cough, and measles vaccinations were begun as well; compulsory diphtheria innoculation began in 1963. Malnutrition was identified as a cause in high childhood morbidity and mortality, relating to a decrease in breastfeeding to only 29% with only about 4% continuing after 3 months; this also caused diarrhea and gastroenteritis. A Breast Feeding Mothers Group was established to help mothers and to support a breast milk bank. In addition the birthrate was very high, 2.8% with very young and elderly mothers giving birth in large numbers and constituting poor obstetric risks. In 1966 the government established a national family planning program. This program, together with nutrition education, improved housing and promotion of breastfeeding has raised the nutrition level. By 1976 the IMR had fallen to 11.8 and the neonatal mortality rate (NMR) was 8.4, both of which were lower than rates in the US, UK, Australia, and New Zealand. In 1981 the IMR fell to 10.8 and the NMR to 7.7. Although deaths from infections and diseases have dropped, those from congenital anomalies and malignancies such as leukemia have not changed. Health education has had an effect on lowering mortality rates from accidents. Rates of death from dengue hemorrhagic fever have been lowered but not abolished by mosquito surveillance, as is the case with other viral infections such as measles. With bacterial infections the latest problem is the existence of antibiotic-resistant strains. Further efforts must emphasize health rather than the reduction of mortality and mental and emotional morbidity must receive more attention as well.
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PMID:Child health in Singapore--past, present and future. 713 9

A phase I trial of diglycoaldehyde (Inox) in children with leukemia established that the maximum tolerated dose of a 5-day schedule was 1.5 g/m2/day. A phase II study was undertaken by the Children's Cancer Study Group to evaluate the efficacy of this dose. Forty-seven children with acute leukemia refractory to conventional forms of therapy were entered in the study: 29 patients with acute lymphocyte leukemia/acute undifferentiated leukemia and 18 with acute nonlymphocytic leukemia. Inox was administered at a dose of 1.5 g/m2 as a 4-6 hour iv infusion daily for 5 days every 14 days. Toxic effects included myelosuppression, proteinuria, nausea, vomiting, diarrhea, local tissue reactions, hypocalcemia, transitory serum amylase elevation, and transitory hypotension. There was one life-threatening episode of drug-related renal toxicity. Of the 27 patients who received a minimum of two courses, partial remissions were observed in two patients with acute nonlymphocytic leukemia. Inox was inactive against advanced acute lymphocytic leukemia.
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PMID:Phase II evaluation of diglycoaldehyde (Inox) in children with acute leukemia: a children's cancer study group report. 742 52

This study compares maximal daily doses of loperamide to escalating doses of continuous intravenous (CI) octreotide acetate in bone marrow transplant (BMT) and leukemia patients. Following chemotherapy, BMT and leukemia patients who developed > or = 600 ml of stool volume in a 24-hr period were randomized to receive loperamide 4 mg po q6h or octreotide 150 micrograms mixed in hyperalimentation solution or normal saline and administered CI. Patients were assessed at 48 hr intervals for decrease in stool volume from baseline. Complete response (CR) was defined as > or = 50% from baseline stool volume (BSV). Patients receiving octreotide who did not achieve a CR at 48 hr were dose escalated by doubling the dose to a maximum of 2,400 micrograms with evaluations at 48 hr intervals. Patients receiving loperamide who did not achieve a CR at 48 hr had treatment discontinued. A total of 36 patients were enrolled in the study. Of these, all were evaluable for intention to treat, and 31 were evaluable for initial response. Based on intent to treat at the initial 48 hr, patients receiving loperamide had a higher complete response rate (86% vs. 45%, P = 0.033) than did those who received octreotide. By treatment analysis (patients who actually received the drug), patients receiving loperamide had a higher complete response rate (92% vs. 56%, P = 0.0448) than did those who received octreotide at the 150 micrograms dosage level. Additional octreotide patients eventually achieved a CR at a higher dosage level (78%). Loperamide at maximal doses of 4 mg po q6h is more effective than octreotide 150 micrograms CI in treating diarrhea following chemotherapy in BMT and leukemia patients. Higher doses of octreotide may be required in a significant number of patients not responding to lower doses.
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PMID:Randomized trial of loperamide versus dose escalation of octreotide acetate for chemotherapy-induced diarrhea in bone marrow transplant and leukemia patients. 748 77

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

Serum samples from 380 cattle were analysed for the presence of bovine immunodeficiency-virus (BIV) antibodies by focus immunoassay (cell-ELISA) and immunofluorescence assay (IFA). All specimens originated from dairy farms in the eastern part of Germany, which had been randomly collected during the period 1989-1991. The cattle were clinically healthy and free of bovine leukaemia virus (BLV) and bovine-virus diarrhoea-virus (BVDV) antibodies. Infection of cell lines with BIV was monitored by syncytia formation, cell-ELISA, and immunofluorescence. The seroprevalence of BIV antibodies was 6.6%, as determined by cell-ELISA. Comparison of IFA and cell-ELISA showed that all IFA positive sera were also positive in cell-ELISA. However, additional sera were reactive only in cell-ELISA. This first report suggests that BIV infection may cause minor problems in German cattle, while BIV is present in a similar prevalence to that reported from other countries.
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PMID:Seroprevalence of bovine immunodeficiency-virus (BIV) antibodies in the cattle population in Germany. 759 62

Carboplatin (CBDCA) is an active agent in the treatment of acute leukemia and is associated with limited extramedullary toxicity. Simultaneous phase II trials were conducted by the Southwest Oncology Group in adult patients with relapsed or refractory acute myeloid leukemia (AML). CBDCA was given as a continuous infusion at a dose of 300 mg/m2 daily for 5 days. Three (8%) of the 37 eligible patients in the relapsed group achieved complete remissions (CRs) lasting 3, 4, and 26 months. Entry of patients was stopped early in the refractory group due to slow accrual and in the relapsed group due to low CR rate. For both groups combined, the CR rate was 3/45 or 7% (95% confidence interval 3-18%). There were 12 fatal toxicities. Four patients died of intracerebral hemorrhage, three of infection, and five of hepatic and/or renal failure. Nonhematologic grade 4 toxicity included diarrhea in three patients, hyperbilirubinemia in four, and mucositis and renal toxicity in one each. These results suggest that CBDCA should not be considered for treatment of relapsed or refractory AML patients with prior high-dose therapy.
Leukemia 1995 Jul
PMID:Carboplatin infusion in relapsed and refractory acute myeloid leukemia--a Southwest Oncology Group trial. 763 Jan 83

Twenty two patients with acute relapsed leukemia (AML 20, ALL 2) were treated with 5-aza-2'-deoxycytidine (DAC) and either m-amsacrine or idarubicin. DAC was administered as a 6-h infusion, every 12 h for 6 days in combination with either m-amsacrine (120 mg/m2) as a 1-h infusion on days 6 and 7 (n = 19) or idarubicin (12 mg/m2) as a 15-min infusion on days 5, 6 and 7 (n = 3). Thirteen patients (59%) achieved a complete remission. The treatment was complicated by nausea, vomiting, diarrhoea with signs of peritonitis (n = 9), weight loss (n = 7), cerebellar or cerebral toxicity (n = 2), gastrointestinal bleeding (n = 3), liver toxicity (n = 2) and prolonged myelosuppression. Median duration of remission was 4 months (range 1-30). The preliminary data show that DAC is an anti-leukemic agent, comparable to high dose Ara-C with comparable severe toxicity.
Leukemia 1993 May
PMID:Preliminary results with 5-aza-2'-deoxycytidine (DAC)-containing chemotherapy in patients with relapsed or refractory acute leukemia. The EORTC Leukemia Cooperative Group. 768 57


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