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)

Aclarubicin (ACR) was administered in a prospective cooperative phase II trial to 44 patients with possibly refractory acute nonlymphocytic leukemia who were previously treated with daunorubicin and cytarabine. Induction treatment consisted of 80 mg/m2 of ACR iv daily for 3 days, followed by 80 mg/m2 iv daily for 2 days in patients not obtaining a complete remission (CR) after 2-4 weeks. CR was observed in eight patients (18%) and partial remission was observed in six (14%). On monthly maintenance chemotherapy with ACR and cytarabine, the duration of CRs varied between 10 and 58 weeks. Achievement of remission was not related to age, presence or absence of Auer bodies, cytogenetic characteristics, or previous response to daunorubicin and cytarabine. Side effects were nausea and vomiting observed in 86% and diarrhea in 34% of the patients, whereas mucositis and alopecia were uncommon. Disturbances of cardiac function arousing suspicion of acute ACR toxicity were observed in seven patients. No case of chronic cardiotoxicity was observed, despite the fact that 20 patients received ACR doses greater than 400 mg/m2, with seven of the 20 having had a previous daunorubicin dose greater than 400 mg/m2. As CR was obtained in four of 14 patients with primary therapy-resistant leukemia and in two of 16 patients with relapse and no response to re-treatment with daunorubicin and cytarabine, ACR does not seem to show clinical cross-resistance to daunorubicin. Evaluation of ACR in first-line chemotherapy of acute nonlymphocytic leukemia appears justified.
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PMID:Aclarubicin in the treatment of acute nonlymphocytic leukemia refractory to treatment with daunorubicin and cytarabine: a phase II trial. 659 2

The physiological pyrimidine nucleoside thymidine (dThd) is cytotoxic to normal and neoplastic cells in culture that are exposed to concentrations in excess of 1 mM for prolonged periods. In order to explore the antileukemic potential of the compound, we have treated six patients with relapsed leukemia or lymphoma with marrow and blood involvement, by prolonged infusions of dThd, at dosages of 90 to 240 g/sq m/day for 14 to 29 days. Mean plasma dThd concentration ranged from 3.8 to 5.5 mM. Cerebrospinal fluid levels were measured on three occasions and ranged from 2 to 23.5% of simultaneous plasma levels. Diarrhea was dose limiting in one patient. The other side effects included nausea and vomiting in all patients, hepatotoxicity in two patients, electrolyte imbalance in one, progression of a pericardial effusion to tamponade in one, and mild central nervous system toxicity in five. In all cases, this therapy produced bone marrow aplasia. One patient with acute lymphoblastic leukemia, refractory to prior treatment, achieved a complete remission which lasted for 16 weeks. Another patient with lymphoblastic lymphoma had a greater than 50% reduction in his mediastinal mass which lasted for less than 1 month. At multiple points during therapy, the bone marrow S-phase fraction was measured by flow cytometry and autoradiography. In five patients, the proportion of cells in S phase increased during the first few days of the infusion but then returned to base line, concomitant with an overall reduction in the number of bone marrow blasts. Cytoreduction was evaluated by the technique of W. Hiddemann, B. D. Clarkson, T. Buchener, M. R. Melamed, and M. Andreeff (Blood, 59: 216-225, 1982). The magnitude of tumor cell kill ranged from 0.7 to 3.6 logs of blasts/cu mm of bone marrow. The data demonstrate that dThd is able to induce a complete remission in a patient with acute leukemia previously refractory to treatment. However, because of the very large drug quantities, fluid volumes, and the prolonged course required to produce the necessary tumor cell kill, this treatment approach is too impractical to be used extensively.
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PMID:Effect of very high-dose thymidine infusions on leukemia and lymphoma patients. 671 7

Metronidazole, in particular, and the other nitroimidazoles (tinidazole, ornidazole) available in Australia are well established drugs for the treatment of protozoal (trichomonal or amoebic) infections; recent data testify to their efficacy in the prevention and therapy of anaerobic infections. Administration by oral and rectal routes is indicated rather than by the intravenous route on the basis of efficacy, safety and cost; this recommendation is applicable to both loading and maintenance dosing. Intravenous administration should be restricted to emergency preoperative loading (single 500-mg dose); to patients with proven anaerobic infections; patients with serious sepsis associated with an unidentified organism; patients who are unable to take medication by mouth and those without a functional rectum or with diarrhoea; and patients with leukaemia who are vomiting. These drugs are remarkably safe under conditions of acute use if the intravenous route is avoided. However, extreme caution in their long-term use and use in obstetric and paediatric patients should be exercised until toxicological issues are resolved. It is concluded that the nitroimidazoles are effective, cheap and safe drugs for the short-term treatment of protozoal and bacterial (anaerobic) infections.
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PMID:Current clinical applications and dose regimens of metronidazole and related nitroimidazoles. 674 31

The pharmacology, chemistry, pharmacokinetics, clinical studies, and adverse effects of amsacrine, an investigational antineoplastic agent, are reviewed. Amsacrine's mechanism of action is not clearly understood, although the drug is known to inhibit DNA synthesis. As an investigational NCI "Group C" agent, amsacrine is available to physicians for the treatment of adult patients with refractory acute nonlymphocytic leukemia (ANLL) under an established protocol. Following intravenous administration, amsacrine has a biphasic plasma clearance. It is extensively metabolized by the liver to inactive compounds that are excreted in the bile. Phase I studies indicated that amsacrine was potentially effective in patients with solid tumors and acute leukemias. Patients with solid tumors could tolerate much lower doses of amsacrine than leukemia patients because of dose-limiting bone-marrow suppression in the former. In Phase II studies, amsacrine appeared effective in treating the acute leukemias, with response rates of 31% and 23% for acute lymphocytic leukemia and ANLL, respectively. Patients with other types of cancers have not responded to amsacrine therapy. Frequently occurring adverse effects of amsacrine include leukopenia and thrombocytopenia in patients with solid tumors; nausea, vomiting, and diarrhea; mucositis in patients receiving higher doses (leukemia patients); alopecia; hepatotoxicity; and phlebitis. The clinical usefulness of amsacrine appears limited to treatment of the acute leukemias. Studies of combination therapies that include amsacrine are currently underway and should further define the therapeutic role of amsacrine.
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PMID:Review of amsacrine, an investigational antineoplastic agent. 676 91

Following allogeneic bone marrow transplantation, graft-versus-host disease (GVHD) develops when the foreign donor lymphoid graft mounts an immunologic reaction against the skin, liver, and gastrointestinal tract of the host. The GVHD syndrome is characterized by skin rash, hepatocellular dysfunction, and secretory diarrhea with destruction of intestinal mucosa. The gastrointestinal radiographic manifestations of proven GVHD were studied in 16 allogeneic marrow recipients transplanted for aplasia (nine) or leukemia (seven). The radiographic findings revealed three distinct phases that correlated with the duration of active gastrointestinal GVHD: (1) Acute phase-seven examinations were performed 4-15 days after the onset of gastrointestinal GVHD, 19-44 days posttransplant. There were simultaneous and uniform changes in the stomach through the small bowel consisting of thickened or flattened mucosal folds, thickening of the bowel wall, rapid transit, and excess luminal fluid. (2) Subacute phase-17 examinations were performed 13-96 days after the onset of gastrointestinal GVHD (40-118 days posttransplant). Abnormalities similar to those of the acute phase were noted, often with a striking segmental distribution. (3) Resolution phase-three patients, who earlier had sequential examinations, were studied when GVHD was no longer clinically active, 43-46 days after the onset of gastrointestinal GVHD (52-94 days posttransplant). These examinations showed improvement, with no abnormalities or effacement of mucosal folds. Mural thickening was confined to the terminal ileum. Gastrointestinal GVHD resolved in the three survivors; it persisted until death in nine of 13. The pathogenic mechanisms and differential diagnosis of the radiographic abnormalities are discussed.
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PMID:Gastrointestinal radiographic features of human graft-vs.-host disease. 678 Dec 55

Ten patients with sepsis and pneumonia complicated by leukemia or lung cancer were treated with cefoxitin (CFX) at daily dose of 6 g. The following results were obtained. 1. Clinical effects of CFX were good in 5 patients, fair in 2 and poor in 3 with effective rate of 50%. 2. Out of 8 patients with sepsis, 5 showed good response to CFX and effective rate was 62.5%. 3. Bacteriological outcomes were eradicated in 1, unchanged in 1, replaced in 2 and unknown in 6 cases. 4. Diarrhea was observed in 1 patient but this was not considered related to CFX therapy. 5. No abnormal laboratory finding due to CFX was observed. 6. It should be considered that 6 g or more of CFX is given in case of severe infections, such as sepsis or pneumonia complicated by serious underlying diseases.
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PMID:[Clinical studies of cefoxitin in the field of internal medicine]. 684 29

This article reports a Phase I study of combined therapy with N-(phosphonacetyl)-L-aspartate (PALA) and L-alanosine in 26 patients with advanced cancer. Each agent exhibits antitumor effect by enzyme inhibition: PALA blocks pyrimidine biosynthesis by impeding aspartate transcarbamylase and L-alanosine depletes purine nucleotides by interfering with adenylosuccinate synthetase. These agents were selected for clinical investigation in light of synergistic cytotoxicity in vitro against human tumor cell lines and in vivo against P-388 murine leukemia resistant to cytosine arabinoside. Dose-limiting toxicities were stomatitis and diarrhea to a lesser extent. There was no substantial myelosuppression. The authors recommend either of two intravenous regimens for studies of therapeutic activity in selected patients with neoplastic diseases: a one-day treatment repeated of PALA, 5.0 g/m2 and L-alanosine, 3.0 g/m2, repeated every 3 weeks; or a monthly program of PALA, 500 mg/m2/d 1-5 and L-alanosine, 60 mg/m2/d 1-5.
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PMID:A Phase I study of the combination N-(phosphonacetyl)-L-aspartate (PALA, NSC-224131) and L-alanosine (NSC-153353) in patients with advanced cancer. 686 Oct 99

Jejunal biopsy specimens from 10 children with acute lymphoblastic leukaemia on methotrexate treatment were compared with 10 from children being investigated for diarrhoea or failure to thrive. In association with methotrexate treatment on both light and electron microscopy, there were marked morphological abnormalities in the villus enterocytes. These consisted of a striking distention of the lateral basal intercellular spaces, cell vacuolation and patchy necrosis and was most marked when methotrexate treatment was given between 24 and 72 h before biopsy. Two mechanisms may be involved: an early direct toxic effect on the mature enterocyte coupled with interference with crypt cell generation, possibly causing ageing and loss of cells proximal to the normal extrusion zone. These pathological changes may account for the malabsorption in association with methotrexate treatment.
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PMID:Small bowel enterocyte abnormalities caused by methotrexate treatment in acute lymphoblastic leukaemia of childhood. 694 49

Two consecutive patients with acute myeloid leukaemia (AML) developed severe probable graft-versus-host disease (GVHD) following transfusion of blood products from normal donors. In one patient the AML had arisen de novo, while in the other it occurred four years after the patient developed non-Hodgkin's lymphoma (NHL) and was treated with radiotherapy and combination cytotoxic chemotherapy. Both patients received anti-leukaemic treatment with doxorubicin and cytosine arabinoside and intensive haematological supportive care with transfusions of red cell, white cell and platelet concentrates obtained from normal donors. Clinically the GVHD in each patient was manifest by a severe erythematous rash, intractable diarrhoea and abnormalities in the liver function tests. On pathological examination the skin in each case showed the typical changes of GVHD. Both patients died. There have been few previous reports of GVHD occurring after accidental engraftment of immunosuppressed patients undergoing therapy for acute leukaemia. Our experience suggests that it may occur more often than has hitherto been recognised. At present there is controversy concerning the possible anti-leukaemic effects of granulocyte transfusions. Until the relative importance of the benefits and deleterious effects of cells with the potential for engraftment is determined by further studies, we recommend the routine irradiation of all cellular blood products intended for administration to acute leukaemia patients undergoing intensive cytoreductive chemotherapy.
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PMID:Graft-versus-host disease in consecutive patients with acute myeloid leukaemia treated with blood cells from normal donors. 694 43

Aclacinomycin A (ACM) is a new anthracycline antibiotic that produces substantially less cardiotoxicity in animals than does doxorubicin. To define the effective dose for the treatment of patients with leukemia, we treated 43 patients with acute nonlymphoblastic leukemia (ANLL) or acute lymphoblastic leukemia (ALL) using ACM administered at three dose levels. All patients had previously received extensive treatment with other chemotherapy; their median cumulative dose of prior anthracycline was 340 mg/m2. An ACM dose of 100 mg/m2/day given for 2 days (total dose, 200 mg/m2) failed to produce significant bone marrow hypocellularity or remission in two patients. Total ACM doses of 300--360 mg/m2 (100 or 120 mg/m2/day x 3 days) produced marrow hypoplasia in 16 to 23 evaluable patients with ANLL. Overall, four of 32 patients with ANLL who received 300--360 mg/m2 of ACM achieved complete remission for duration of 1, 5+, 6 and 15+ months. Two of nine patients with ALL achieved partial remission. Toxic effects of this therapy included severe leukopenia and thrombocytopenia, nausea, mucositis, and diarrhea. ECG abnormalities were noted in 43% of patients who were carefully monitored; however, only one patient developed a significant decrease in left ventricular ejection fraction as measured by radionuclide cardiography. ACM produced only minimal alopecia and did not cause tissue necrosis following inadvertent subcutaneous infiltration. We conclude that 300--360 mg/m2 of ACM is an effective dose for the treatment of patients with ANLL and that further evaluation of this compound is indicated in patients who have received minimal prior therapy.
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PMID:Phase I--II evaluation of a new anthracycline antibiotic, aclacinomycin A, in adults with refractory leukemia. 695 22


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