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

verapamil, a calcium-influx blocker, enhanced the cytotoxicity of vincristine (VCR) in vitro 6- to 12-fold in eight human hemopoietic tumor cell lines established from acute lymphatic leukemia, acute myelogenous leukemia, and Burkitt's lymphoma. Great enhancement of VCR cytotoxicity was obtained in a VCR-resistant subline of K562 myelogenous leukemia. A maximum of approximate 100-fold increase in VCR cytotoxicity occurred. Heterogeneity in VCR sensitivity (80-fold difference in sensitivity) was observed in vitro among these human tumor cells. BALL and Daudi cells of B-cell type were more susceptible to VCR. At 6.6 or 20 microM of verapamil, the values for the concentration of drug required for 50% inhibition of cell growth for each cell line fell into a rather narrow range, and heterogeneity in VCR sensitivity among cell lines was circumvented in vitro. Verapamil also enhanced the cytotoxicity of Adriamycin, although the extent of enhancement was considerably small. Enhancement of VCR cytotoxicity also occurred with other calcium antagonists and calmodulin inhibitors. At maximum effective concentration of these reagents, a 3- to 5-fold increase in VCR cytotoxicity occurred in K562 cells. In VCR-resistant K562 cells, a more prominent enhancement (20- to 45-fold) was observed with these reagents. VCR resistance was circumvented in vitro. The mechanism of enhancement of VCR cytotoxicity was explained by the enhanced accumulation of VCR in K562, especially in resistant cells.
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PMID:Potentiation of vincristine and Adriamycin effects in human hemopoietic tumor cell lines by calcium antagonists and calmodulin inhibitors. 683 50

Five hundred forty three adult patients with acute leukemia were entered on the study designed to: (1) test efficacy of vincristine and prednisone used as primary drug therapy in patients with good prognosis as judged by a circulating blast cell count less than 30,000 cm2; (2) investigate the use of either simultaneously or sequentially administered Adriamycin plus cytosine arabinoside plus vincristine and prednisone; and (3) to assess the use of bacillus Calmette-Guerin (BCG) in the maintenance phase on both the response and duration of response. Complete remissions were seen in 21% of patients with the vincristine and prednisone arm. Complete remission rates were similar in both the simultaneously and sequentially administered chemotherapy with overall complete remission rates of 55%. Median durations of complete remission and survival were 35 and 62 weeks, respectively, for patients with AML; and 47 and 75, respectively, for patients with ALL. Toxicity was within acceptable limits. BCG administered during the maintenance phase of therapy caused no differences in duration of complete remission and survival. These results demonstrate an improved response and duration of response over previous studies done by this group.
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PMID:Management of adult acute leukemia. A Southwest Oncology Group study. 688 80

Eighty-six consecutive untreated adults with acute myelogenous leukemia were treated with a combination of Adriamycin, vincristine, prednisolone, Cytosine Arabinoside, and BCG. Complete remission was achieved in 39 (45%) patients; these patients were then allocated on an alternate basis to receive BCG and monthly chemotherapy with or without weekly irradiated allogeneic blast cells. The median duration of remission was eight months and was the same for both groups. The median survival of those achieving complete remission was 19 months compared with two months for those not achieving complete remission. Nine patients are still alive without relapse and five of these patients have been disease free for more than three years.
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PMID:Chemotherapy and immunotherapy for acute myelogenous leukemia. 693 92

Sixty-two adult patients with acute myeloid leukemia were treated with a chemotherapy program of Adriamycin, Cytosine Arabinoside (Ara-C), vincristine, and prednisone (Ad-OAP). Immunotherapy with BCG by scarification was administered before and/or during remission induction therapy. Maintenance chemoimmunotherapy consisted of Ara-C, vincristine, prednisone, and BCG. Patients still in remission after 12 months received late intensification chemotherapy for three courses before discontinuing chemotherapy. Forty-four (71%) patients achieved a complete remission (CR). The CR rate for patients less than 50 years of age ws 84% (32/38). Age was strongly predictive for response and survival. An additional 14 patients with acute lymphoid leukemia were treated with the same program; ten patients responded, all have relapsed and died. Nine patients with AML remain alive 4 1/2-6+ years from diagnosis.
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PMID:Chemoimmunotherapy of adult acute leukemia. 693 77

Combination chemotherapy with an anthracycline, Adriamycin or rubidazone, cytosine arabinoside, vincristine and prednisone resulted in a complete remission rate of 62% in 325 consecutive unselected adults with acute leukemia. The results by morphologic categories were 58% for acute myelogenous leukemia (AML), 70% for acute undifferentiated leukemia (AUL), and 77% for acute lymphoblastic leukemia (ALL). The median survival was 43 weeks. Ten percent of all patients are projected to be alive and in remission at five years. The median remission duration for the whole group was 51 weeks, durations being significantly longer for AML (60 wks) than ALL (30 wks) and AUL (21 wks). Central nervous system involvement was uncommon in AML (4%), but much more common in patients with AUL (37%) and ALL (32%). One in five complete responders with AML is projected to be in their first remission at five years off all chemotherapy. Age, sex, morphology, cytogenetic pattern, temperature of presentation, and presence of a documented preceding hematologic abnormality are found to be significant variables for response and survival.
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PMID:A four-year experience with anthracycline, cytosine arabinoside, vincristine and prednisone combination chemotherapy in 325 adults with acute leukemia. 694 6

A review is presented of experimental information pertaining to the characteristics of a procedure designed to quantitate the capacity for self-renewal in clonogenic cells of human acute myeloblastic leukemia. In a series of 44 previously untreated patients, a significant correlation (p less than 0.01) was seen between low capacity for self-renewal and successful remission induction. Three cytotoxic drugs (Adriamycin, 1-beta-D-arabinofuranosylcytosine, and N-[4-(19-acridinylamino)-3-methoxyphenyl]-methanesulfonamide) were tested for preferential effect against self-renewal events. Surviving clonogenic cells to these agents had, respectively, unchanged, lower, and higher capacity for self-renewal. The implications of such drug properties are discussed.
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PMID:Self-renewal capacity of leukemic blast progenitor cells. 694 8

Leukemia cells from 4 acute myelocytic leukemia (AML) and 1 acute lymphocytic leukemia (ALL) patients were incubated with a set of 6 anthracycline agents: Adriamycin (Am), 4'-epi-Adriamycin (4'-epi-Am), daunorubicin (Dm), 4-demethoxy-daunorubicin (4-dDm), carminomycin (Cm) and N-trifluoroacetyl-Am-14-valerate (AD32). Cells were assayed for drug uptake after incubation for 2 h, and for DNA damage and drug retention 4 h later. Uptake and retention patterns were characteristic for each agent and fairly uniform for the different cell populations. In contrast, profiles of the amount of DNA damage produced reflected striking differences in each population of cells. These individual responses raise the possibility that leukemic cells resistant to one anthracycline may yet be sensitive to another.
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PMID:DNA damage by anthracycline drugs in human leukemia cells. 694 56

The in vitro sensitivity of leukemic colony-forming cells to Cytosine arabinoside (Ara-C) was assessed in acute myeloid leukemia, by means of a clonogenic assay using methyl-cellulose with phyto-hemagglutinin (PHA)-leukocyte conditioned medium. Bone marrow clonogenic cells were more sensitive to Ara-C than blood clonogenic cells. Also a continuous exposure to Ara-C induced a higher reduction of the leukemic colonies than one hour exposure. Patients were, according to the in vitro results, divided into 3 groups: eight patients had a dose-responsive curve for all the tested drug concentrations and were characterized by a marked sensitivity to the induction treatment combining Ara-C and Adriamycin. Three patients had a = 50% reduction of colonies with the 3 concentrations; two achieved complete remissions. Seven patients were in vitro insensitive to the drug; four of them had a relative or absolute resistance to the induction treatment.
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PMID:In vitro sensitivity of CFU-L to cytosine arabinoside (Ara-C). 696 23

We have treated two pediatric patients with refractory ANLL and four with relapsed high-risk ALL with Adriamycin continuous Ara-C i.v. Four out of six patients were able to enter complete remission after first or second course of the treatment. All of them developed severe bone marrow suppression, and various degree of oral mucositis, liver dysfunction and gastrointestinal toxicity, and two patients died from side effects. Recently this combination chemotherapy is becoming a best regimen for the treatment of untreated ANLL. Although our cases are small in number, this combination therapy also seems to be effective for refractory ANLL and relapsed high-risk ALL. It is needless to say that we have to pay more attention when we use this regimen.
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PMID:[Adriamycin and Ara-C infusions in the treatment of refractory leukemia]. 696 38

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.
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PMID:A prognostic factor analysis for use in development of predictive models for response in adult acute leukemia. 709 87


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