Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pretreatment characteristics of 325 adults with acute leukemia who were treated at the M. D. Anderson Hospital between 1973 and 1977 have been evaluated to assess their value as prognostic indicators. The patient population includes all patients treated with an anthracycline (Adriamycin or rubidazone), cytosine arabinoside, vincristine, and prednisone during the time period. Most patients had one of the variants of acute myelogenous leukemia (75%), and the remaining patients had acute lymphoblastic leukemia (16%) or undifferentiated leukemia (8%). Twenty-one factors were found to be significantly associated with probability of obtaining a complete response. In addition to characteristics previously known to provide prognostic information such as age, temperature status at the start of treatment, morphology, the presence of Auer rods, sex, and hemoglobin level, we identified the presence of a documented antecedent hematologic disorder and the finding of insufficient metaphases on cytogenetic analysis using the squash technique as being major prognostic variables. In addition, the pretreatment biochemical characteristics of hypoalbuminemia and elevated blood urea nitrogen and creatinine were found to adversely influence prognosis. The prognostic significance of factors such as the leukocyte count and platelet count, identified in earlier studies, was not confirmed in this group of patients. From this natural-history analysis predictive models for response have been developed using multivariate logistic regression techniques. One of these models has been used to evaluate the effect of morphology, treatment, and cytogenetic pattern on response to the combination of drugs used.
 ...
PMID:A prognostic factor analysis for use in development of predictive models for response in adult acute leukemia. 709 87

The purpose of the study was to analyze the clinical and laboratory characteristics of patients with acute lymphocytic leukemia (ALL) who exhibited myeloperoxidase-positive blasts by electron microscopy (EM-MPO-positive), and assess their response to therapy and their prognosis. Since 1988, 21 adults with newly-diagnosed ALL and EM-MPO-positive blasts were referred to our service. In addition to documentation of their clinical and hematopathologic characteristics, patients underwent cytogenetic, immunophenotypic, molecular, and electron-microscopic evaluations. Twenty patients were treated with the vincristine-Adriamycin-dexamethasone (VAD) regimen, and one patient was induced with amsacrine and high-dose cytosine arabinoside (ara-C). The 21 patients were among 141 patients with ALL (15%) seen during the same period. Their median age was 46 years (range 15 to 77 years). The immunophenotype was T-cell ALL in 12 patients (57%). Karyotypic studies did not demonstrate specific recurrent abnormalities. The median percentage of EM-MPO-positive blasts was 15% (range 3% to 45%). Eighteen patients (85%) had high-risk ALL. With induction chemotherapy 15 of 20 (75%) receiving VAD therapy achieved a complete remission (CR). However, the median CR duration was 18 months, and the median survival was 18 months with a 3-year disease-free survival rate of 25%. There were eight relapses and one lineage switch to acute myelogenous leukemia (AML). Patients with ALL and EM-MPO-positive disease are a unique subgroup with long-term poor prognosis on conventional anti-ALL therapy, and may benefit from intensification treatments with agents effective against AML.
 ...
PMID:Characteristics and outcome of patients with acute lymphocytic leukemia and myeloperoxidase-positive blasts by electron microscopy. 786 Apr 34

The elimination kinetics of the alkylation product O6-ethylguanine (O6eGua) from nuclear DNA were determined in individual lymphocytes or blast cells isolated from 27 patients with chronic lymphatic leukemia (CLL) and 26 patients with de novo acute myeloid leukemia (AML). A monoclonal antibody-based immunocytological assay was used for quantification of O6eGua in DNA of individual cells after pulse exposure of cells to N-ethyl-N-nitrosourea (EtNU). In cell specimens from a given patient, no major subpopulations with significantly different capacities for repair of O6eGua were observed. The time required to remove 50% of induced O6eGua residues varied interindividually between 0.5 and 8.4 h in CLL lymphocytes and between 0.8 and 6.3 h in leukemic blast cells. An inverse relationship was found between the rate of removal of O6eGua from DNA and the chemosensitivity of cells to EtNU, 1,3-bis(2-chloroethyl)-1-nitrosourea or mafosfamide in vitro. High rates of O6eGua repair and pronounced resistance to mafosfamide, 1,3-bis(2-chloroethyl)-1-nitrosourea, and EtNU in vitro were found in samples from 8 CLL patients nonresponsive to chemotherapy with alkylating agents. In AML patients treated with anthracyclines and 1-beta-D-arabinofuranosylcytosine, no relation was found between DNA repair capacity and treatment outcome. However, increased P-glycoprotein expression was observed between specimens derived from AML patients who had failed to reach complete remission (n = 12) after chemotherapy versus responsive patients (n = 14). DNA repair rate was not related to chemosensitivity to Adriamycin and 1-beta-D-arabinofuranosylcytosine in vitro, nor were cellular glutathione content, glutathione S-transferases activity, or P-glycoprotein expression.
 ...
PMID:Capacity of individual chronic lymphatic leukemia lymphocytes and leukemic blast cells for repair of O6-ethylguanine in DNA: relation to chemosensitivity in vitro and treatment outcome. 804 3

Combination therapy with idarubicin plus continuous-infusion, high-dose cytarabine in patients with newly diagnosed acute myelogenous leukemia resulted in an improved complete response rate over historic controls who received either (1) Adriamycin or amsacrine in combination with standard-dose cytarabine or (2) continuous-infusion, high-dose cytarabine alone or in combination with amsacrine or mitoxantrone. The complete response rate in patients with acute myelogenous leukemia was similar to that in patients with refractory anemia with excess blasts in transformation.
 ...
PMID:Idarubicin plus continuous-infusion high-dose cytarabine as treatment for patients with acute myelogenous leukemia or myelodysplastic syndrome. 829 Sep 66

A total of 107 patients with newly diagnosed acute myeloblastic leukemia (AML) were referred to the ICRF Department of Medical Oncology at St Bartholomew's Hospital between August 1986 and July 1989. Of those referred, 92 (87%) were treated with remission induction chemotherapy comprising: Adriamycin, cytosine arabinoside (ara-C) and 6-thioguanine if aged < 60 years (57 patients) or mitoxantrone (MTN) and ara-C if aged > 60 years (35 patients). Of those treated, 54 (58%) entered complete remission (CR). Recurrent AML developed in 38 out of these 54 patients (70%) of whom 25 aged 19-73 years (median 50 years) subsequently received MTN and ara-C as reinduction therapy. The 19 younger patients (under 60 years old) received MTN at 12 mg/m2, intravenously, daily for 5 days and ara-C at 100 mg/m2, intravenously, twice daily for 7 days. The six older patients received the same ara-C schedule but the dose of MTN was reduced to 10 mg/m2 for 5 days. Second CR was achieved in 16 out of 25 patients (64%) [12/19 (63%) and 4/6 (67%) for patients aged under or over 60 years, respectively]. Eight of the patients in whom second CR was achieved were aged under 50 years and were thus eligible for additional consolidation comprising myeloablative therapy with autologous bone marrow transplantation (ABMT). Four patients actually received the latter treatment: two remain in second CR at 21 and 46 months. Three of the remaining eight patients aged > 50 years in whom second CR was achieved remain in second CR 8 to 43 months later. Censored for myeloablative therapy + ABMT, the overall median duration of second CR was 5 months. Although remissions tended to be short, in younger patients the possibility of proceeding to myeloablative therapy with autologous bone marrow support makes the regimen worthwhile and, even in older patients, it was sometimes possible to achieve prolonged second remissions.
 ...
PMID:Mitoxantrone and cytosine arabinoside as treatment for acute myelogenous leukemia (AML) at first recurrence. 841 9

Thirty children presenting with acute nonlymphoblastic leukaemia from June 1984 to December 1989 were treated at one UK centre using a West German protocol, AML-BFM-83. This consisted of Induction, an intensive outpatient-based Consolidation regimen with seven different drugs and cranial irradiation, and Continuation therapy with thioguanine and cytosine arabinoside for 2 years with additional Adriamycin in the first year. Twenty-five children achieved complete remission (83%). There were two early deaths from haemorrhage and infection and three from Induction failure. After a median follow-up time of 60 months, nine relapses have occurred, all in the bone marrow. Life table analysis revealed a probability for survival at 5 years of 47%, event-free survival 43%, and event-free interval 50%. Median bed occupancy for chemotherapy and toxicity was 41 days, with median hospital stays of 29 days for Induction, 11 days for Consolidation and less than 1 day for Continuation. This data suggests that long-term remissions can be achieved in just under half of children with acute nonlymphoblastic leukaemia while creating only modest demands on inpatient resources.
 ...
PMID:Treatment of childhood acute myeloid leukaemia using the BFM-83 protocol. 842 81

The MDR1 gene is involved in drug resistance in many hematopoietic and solid tumors. The Quantitative PCR System 5000 (QPCR-5000; Perkin-Elmer) is a new instrument system that uses electrochemiluminescence to automatically quantitate polymerase chain reaction (PCR) products. A comparative study between radioactively labeled PCR (32P-PCR) and QPCR was performed to analyze the MDR1 gene expression in the drug-resistant (Doxorubicin) cell lines Dox40, Dox6, the parental cell line 8226/S, CEM Dox1 and three acute myeloid leukemia (AML) patient samples. Using the Dox40 and Dox6 resistant cell lines, we compared the sensitivities of QPCR and 32P-PCR. A strong signal was obtained from QPCR at 20 to 25 cycles (which is in the linear range for quantitation), while a weak signal was obtained using 32P-PCR at the same cycle number. Dilution experiments gave better precision with the QPCR than with the radioactive method. AML samples were studied with the MDR1-specific MAbs MRK16 and 4E3, and the efflux function was analyzed using Rh-123 retention in the absence or presence of verapamil. The three samples showed high (D = 0.79), medium (D = 0.52) and negative (D = 0.08) p-glycoprotein (P-gp) levels and correlated with efflux function. The MDR1/beta 2-M mRNA ratios for 32P-PCR were 0.41, 0.40 and 0.12, respectively, and were 0.127, 0.097 and 0.028, respectively, for QPCR. There were significant differences between the samples with high and medium P-gp levels comparing the two methods. Very low levels of MDR1 in CEM Dox1 cells could be detected only by QPCR. In conclusion, QPCR was found to be more reproducible, accurate and sensitive than 32P-PCR.
 ...
PMID:Semi-automated PCR method for quantitating MDR1 expression. 889 Dec 27

32 patients of denovo-ANLL were treated with Doxorubicin, Ara-C and 6-Mercaptopurine (DAM) regimen. Remission induction was instituted with 1-3 cycles of DAM regimen and maintenance was given by 6-MP continuously with intermittent DA (1,5) regimen. In the remission induction, Doxorubicin 30 mg/m2 for 3 days, Ara-C 150 mg/m2 for 5 days and 6-Mp 100 mg/m2 daily was given. Complete remission (CR) was observed in 60% cases. The probability of 2 years disease-free survival of patients with complete remission is 56.73%.
 ...
PMID:Chemotherapy of acute myeloblastic leukaemia with DAM regimen. 962 77

Radiochemotherapy-resistant blasts commonly cause treatment failure in acute myeloid leukemia (AML), and their resistance is due, in part, to overexpression of multidrug resistance (mdr) proteins. We reasoned that targeted delivery of protein synthesis inactivating toxins to leukemic blasts would reduce the cellular concentrations of relatively short half-life resistance proteins and sensitize the cells to cytotoxic drugs. To test this hypothesis, we employed human granulocyte-macrophage colony-stimulating factor fused to truncated diphtheria toxin (DT388-GMCSF). The human AML cell line HL60 and its vincristine-resistant sublines, HL60Vinc and HL60VCR, were incubated in vitro for 24 h with varying concentrations of toxin. Doxorubicin was added for an additional 24 h, and cell cytotoxicity was assayed by thymidine incorporation and colony formation in semisolid medium. DT388-GMCSF sensitized HL60Vinc and HL60VCR but not HL60 to doxorubicin. Combination indices for three log cell kill varied from 0.2 to 0.3. In contrast, pretreatment with doxorubicin followed by toxins failed to show synergy. At least in the case of the vincristine-resistant cell lines, modulation of drug resistance correlated with reduction in membrane P-glycoprotein concentrations based on immunoblots with C219 antibody, flow cytometry with MRK16 antibody, and cell uptake of doxorubicin. These observations suggest clinical trials of combination therapy may be warranted in patients with refractory AML. Further, targeted toxins may represent a novel class of cell-specific modulators of drug resistance for a number of malignancies.
 ...
PMID:Cell-specific modulation of drug resistance in acute myeloid leukemic blasts by diphtheria fusion toxin, DT388-GMCSF. 966 51

Acute myeloid leukemia (AML) is the most common form of acute leukemia. Contemporary chemotherapy regimens fail to cure most patients with AML. We have genetically engineered a recombinant diphtheria toxin human granulocyte macrophage colony-stimulating factor (GMCSF) chimeric fusion protein (DTctGMCSF) that specifically targets the GMCSF receptor on fresh human AML cells and myeloid leukemia cell lines. At a nontoxic dose level, DTctGMCSF therapy was superior to the standard chemotherapeutic agents 1-beta-D-arabinofuranosylcytosine and Adriamycin, resulting in 60% long-term event-free survival of severe combined immunodeficient mice challenged with an otherwise invariably fatal cell dose of the human HL-60 myeloid leukemia. Notably, systemic exposure levels of DTctGMCSF, which were found to be therapeutic in the severe combined immunodeficient mouse xenograft model of human HL-60 myeloid leukemia, could be achieved in cynomolgus monkeys without any significant nonhematological toxicities. The recombinant DTctGMCSF fusion toxin might be useful in the treatment of AML patients whose leukemias have recurred and developed resistance to contemporary chemotherapy programs.
 ...
PMID:In vivo biotherapy of HL-60 myeloid leukemia with a genetically engineered recombinant fusion toxin directed against the human granulocyte macrophage colony-stimulating factor receptor. 981 18


<< Previous 1 2 3 4 5 6 7 8 Next >>