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)

The results of the administration of two antimetabolites, methotrexate (MTX) and cytosine arabinoside (Ara-C), for the prevention and treatment of established central nervous system (CNS) disease in children with acute lymphoblastic leukemia are discussed. Two protocols (L-2 and L-10) for the management of patients with acute lymphoblastic leukemia have been developed. In the L-2 protocol, prophylaxis consists of repeated intralumbar injections of MTX alone, and in the L-10 regimen, both MTX and Ara-C are administered; for the patients with an initial leukocyte count of greater than or equal to 25,000/mm3, the two drugs are given intraventricularly instead of by the usual intralumbar route. In the treatment of established CNS leukemia, intralumbar MTX and Ara-C in addition to CNS irradiation are employed; for maintenance, periodic intraventricular MTX injections are given. Of the 70 children receiving the L-2 protocol, four developed CNS leukemia and in a fifth patient, CNS and bone marrow relapse were concurrent. Among the 31 children receiving the L-10 regimen, CNS disease has been observed in only one child. Of the five children treated for the established CNS leukemia, recurrence was observed in two at 19 and 29 months after remission; the other three remain in remission for 2, 15, and 39 months, respectively.
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PMID:Antimetaboliths in the prophylaxis and treatment of central nervous system leukemia. 26 7

Leukaemia cells from the peripheral blood and bone marrow of patients with acute myeloblastic leukaemia were labelled in vitro with [125I]5-iodo-2'-deoxy-uridine (IUdR). The myeloblasts were then injected into groups of mice and the survival of these cells estimated by measuring isotope loss, using whole-body counting. The isotope excretion from mice treated with various doses of cytosine arabinoside (Ara-C) and those not treated with drugs were compared. This comparison showed that the sensitivity of myeloblasts to the drug varies from patient to patient, and in one case was different for myeloblasts from bone marrow and from blood from the same patient. We compare the clinical responses of myeloblasts to Ara-C in 6 patients, who had high peripheral blood myeloblast counts, with the sensitivities of their myeloblasts to Ara-C in mice. This comparison indicates that the assay might be a useful way of predicting the response of leukaemic cells in patients to cytotoxic agents.
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PMID:Assessment of drug sensitivity of human leukaemic myeloblasts. II. The toxic effects of cytosine arabinoside on 125IUdR-labelled human leukaemic myeloblasts in mice. 27 Mar 73

Tumor cells were isolated from malignant effusions of three patients with disseminated solid tumors of different origin. Intracellular accumulation of nondiffusible cytosine arabinoside (ara-C) nucleotides was used to measure phosphorylation. Mouse leukemia L 1210 and L 1210/CA, and ara-C-resistant subline, were used as reference cells. Phosphorylation activity was similar in the cells from all three solid tumors and showed a linear increase with drug concentrations of 0.1--100 micograms/ml. In contrast to activity in L 1210 cells, the in vitro activity was not saturable at drug levels up to 100 micrograms/ml. Ara-C inhibited the incorporation of thymidine into DNA 84%--90% in the solid tumor cells at a concentration of 10 micrograms/ml. Higher drug concentrations did not result in further inhibition. In one patient, DNA synthesis of tumor cells isolated before and after intraperitoneal instillation of 1,000 mg ara-C was measured. The in vivo inhibition was found to correspond to the in vitro data. Solid tumor cells isolated from malignant effusion have no greatly reduced capacity for cellular formation of ara-C/nucleotides, but higher drug levels than achieved with conventional therapy are necessary for sufficient ara-C nucleotide synthesis.
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PMID:Action of cytosine arabinoside on human tumor cells isolated from malignant effusions: in vitro phosphorylation and inhibition of DNA synthesis. 48 20

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

In two patients with acute leukaemia, the development of progressive interstitial pulmonary fibrosis was observed following chemotherapy with BCNU, Cytoxan and Ara-C. The x-ray changes were accompanied by restrictive changes of pulmonary function and, later on, by severe hypoxia. Serologic tests did not reveal infection with cytomegaly virus or mycoplasma pneumoniae. These findings, together with reports in the literature, suggest a toxic effect of BCNU on the lung. The combination with Cyclophosphamide may contribute to this toxic reaction.
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PMID:[Progressive pulmonary fibrosis during combination chemotherapy with BCNU (author's transl)]. 65 38

One hundred forty-three children with refractory lymphoblastic and undifferentiated leukemia (ALL/AUL) were treated with cytosine arabinoside (Ara-C) and prednisone (Pred). The dose and duration of Ara-C was escalated during induction depending on the response seen in the peripheral blood and/or bone marrow. For those achieving a remission, Ara-C was also used to determine its maintenance capabilities. Of the 143 children, 79 attained a clinical remission, 45 having a complete bone marrow remission and 34 having a partial remission. Maintenance of remission with twice weekly Ara-C was short and did not appear to depend on the amount of Ara-C given during induction. The major toxicity of Ara-C was myelosuppression.
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PMID:Usefulness of cytosine arabinoside (NSC-63878) and prednisone (NSC-10023) in refractory childhood lymphoblastic leukemia. 106 43

No more than 150 cases of neonatal leukemia had been reported in the literature. Seven additional cases are reported herein. The incidence of neonatal leukemia has been of one in 50,000. Its incidence among the group of neonates requiring hospitalization has been of 0.075%. The seven neonates with leukemia consist of five males and two females. Two of them had an associated Down's syndrome. Abdominal distension, hepatomegaly, splenomegaly, cutaneous manifestations and purpura were the most frequent clinical findings in our patients. Severe anemia was present in only three patients. Thrombocytopenia was recognized in six of them. A high white blood cell count was present in five patients. The number of blast cells in their peripheral blood smear ranged between 16 and 100%. A remarkable myeloid dominance was observed. One patient died two hours after birth and his diagnosis was made at autopsy. Three patients were diagnosed before the age of three weeks. The three patients with myeloid leukemia were treated with DNR and Ara-C. A complete hematological remission was achieved in two of them. One patient died of a Pn. carinii pneumonia one month after the remission was induced. The remainder patient of this group had a Down's syndrome and the leukemia had been confirmed by hepatic biopsy. After two years of maintenance with Ara-C and Thioguanine he is alive and both, peripheral blood and bone marrow, remains normal. A lymphocitic leukemia was seen in only two patients. One was treated with prednisolone and VCR, and the other with prednisolone, VR and L-Asp. In both cases a good response to the chemotherapy was observed. Autopsy was performed in all patients who died but one. The pathological findings are analyzed. The low survival among patients with neonatal leukemia may be influenced by the toxic side effects of the used chemotherapy. All aspects of the medical treatment including drugs of choice and the usefullness of isolation devices are further discussed.
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PMID:[Neonatal leukemia. Report of seven cases (author's transl)]. 106 63

Recent studies in this laboratory have been directed at investigating the cellular and subcellular metabolism of RNA in leukemic cells which have been characterized with respect to their degree and type of sensitivity/resistance to specific chemotherapeutic agents. In the present report, electrophoretic patterns on several types of SDS-polyacrylamide gels are presented using total cellular RNA preparations from a subline of L1210 mouse leukemia found to be resistant to cytosine arabinoside (L1210/Ara-C). These studies have been facilitated by using a computerized-spectrophotometric system for quantitative and qualitative comparisons of these profiles. The results suggest that patterns of RNA metabolism may be a useful biochemical test in leukemia.
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PMID:Biochemical profiles of cancer cells: I. Computerized analysis of mouse leukemic cellular RNA on polyacrylamide gels. 112 77

Of 4 lines of myelogenous rat leukemias induced by N-nitrosobutylurea (NBU), DBLA-6 was selected as a screening model for antileukemic agents because of the following characteristics: a) High transplantability either by intravenous (i.v.) or intraperitoneal (i.p.) inoculation; b) linear relationship between inoculum size and survival time; c) marked increase of leucocyte counts in the peripheral blood as the tumor progresses after intravenous inoculation. To investigate reliability in its predicting clinical efficacy, its sensitivity to known antileukemics was studied. To determine the effects, a change of leucocyte counts in the peripheral blood together with the prolongation of life span was checked in the following systems; i.v.-i.v. (i.v.-inoculation, i.v.-injection), i.v.-i.p., i.p.-i.p., i.p.-i.v. Fifty percent cure was obtained with Vincristine, Vinblastine, Daunorubicin, 6-Mercaptopurine, and alkylating agent 838D or 864T. The success of treatment was measured by decrease of leucocytes. Methotrexate, cytosine arabinoside (Ara-C), and cyclophosphamide showed only poor effects, and Mitomycin C, L-asparaginase, and Bleomycin were ineffective. In addition, the chemotherapeutic effects of Vincristine and 864 on this leukemia were quite dependend both on the route of drug injection and on the site of tumor inoculation. Subsequently, our studies are being extended to cover the correlation between drug distribution and tumor localization or dissemination.
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PMID:Sensitivity of DBLA-6 leukemia of rats to known antitumor agents in relation to their clinical effects. 116 99

A series of 30 unselected patients with acute nonlymphoblastic leukemia (ANLL) was treated with combination chemotherapy, including three courses of cytosine arabinoside (Ara-C) by 5-day continuous i.v. infusion, vincristine i.v. weekly, and prednisone daily to complete remission. Ara-C was administered alone as a 5-day continuous i.v. infusion monthly for maintenance. Ten (33%) achieved a complete remission (CR). The remaining 30 (67%), including temporary partial remissions, hematologic improvements, inadequate trials, and early deaths, were all considered failures. The CR rate was 57% in those 17 cases receiving an adequate trial. After After 5 1/2 years' followup, the overall median survival, including cases failing to achieve CR, was 3.1 months. For those having adequate trials the median survival was 16.6 months, and for those achieving a CR, 36.6 months. Two patients are still alive, one at 55.2 months on maintenance therapy, and the other at 62.8 months, currently unmaintained.
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PMID:The role of cytosine arabinoside maintenance in acute nonlymphoblastic leukemia. 118 75


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