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)

The authors developed a therapeutic regimen in which 33 patients aged 11 to 61 years (mean +/- SE, 35.9 +/- 2.3 years) with acute myeloid leukemia (AML) were given intensive induction chemotherapy with Adriamycin (doxorubicin) (ADM), vincristine (VCR) and cytosine arabinoside (ARA-C). Twenty-nine of these patients (88%) attained a complete remission (CR) after 1, 2, or 3 courses and were then subjected to an early consolidation course of chemotherapy, identical to that for induction. After consolidation, all patients in CR received a long-term continuous maintenance therapy in which 6-mercaptopurine (6-MP) and methotrexate (MTX) were alternated, associated with periodic reinforcements with daunorubicin (DNR) and VCR. Twenty-five of the 29 patients who achieved a CR were splenectomized soon after the consolidation course. Histologic sections of the spleens, liver biopsy specimens, and lymph nodes, stained routinely and with the naphthol AS-D chloroacetate esterase (NCA) method, showed mature granulocytes and a few NCA positive mononuclear cells, but no proved leukemic infiltrates. For the 25 splenectomized patients, the probability of remaining in CR at 36 and 54 months was 75% and 66%, respectively; the probability of survival at 36 and 54 months was 85% and 75%, respectively. Age older than 40 years and evidence of extramedullary involvement at presentation appeared to carry a bad prognosis for disease-free survival.
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PMID:Treatment of acute myeloid leukemia with a combination of intensive induction chemotherapy, early consolidation, splenectomy and long-term maintenance chemotherapy. 658 96

Ten AML- and two MDS-patients in whom conventional chemotherapy was contraindicated or ineffective were treated with low dose ARA-C, 10 mg/m2 per 12hS.C. for 2-4 weeks. Seven patients obtained a complete and two a partial remission. Our findings suggest that low dose ARA-C may act both by induction of differentiation and/or inhibition of proliferation.
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PMID:Low-dose cytosine-arabinoside in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). 658 41

Thirteen patients with acute myeloid leukaemia aged from 19 to 81 were treated with low dose cytosine arabinoside (ARA-C) in a dose of 10-15 mg/m2 twice daily subcutaneously. Three complete remissions were obtained. Partial responses were observed in a further two patients. To analyse the action of low dose ARA-C freshly isolated leukaemic cells and cells from the cloned promyelocytic leukaemia cell line (HL60) were cultured in vitro in the presence of cytosine arabinoside. Minimal evidence of differentiation induction was observed when compared with the cytotoxic effects of the drug. These results suggest that ARA-C does not exert its anti-leukaemic effects by halting proliferation through differentiation induction. Rather, it appeared that the capacity of this agent to kill cells in S-phase produced a progressive depletion of the cycling leukaemic cells. This resulted in a corresponding steady decline in the total leukaemic cell population.
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PMID:Low dose cytosine arabinoside: partial remission of acute myeloid leukaemia without evidence of differentiation induction. 658 3

As an in vitro model for the chemotherapy of acute myeloid leukemia with cytarabine (ARA-C), the cytotoxicity of this drug was investigated using a human promyelocytic cell line (HL-60) and different drug schedules. The continuous exposure to ARA-C was shown to be more cytotoxic than the intermittent exposures at identical concentrations or under conditions where the concentrations multiplied by time of exposure were the same. In a comparison of exposures, as the intervals between drug exposures were reduced, the cytotoxicity of ARA-C increased. Flow microfluorometric analysis of DNA content showed that a 3-hour exposure to ARA-C every 6 hours produced a greater accumulation of cells in S phase than the same exposure repeated every 12 hours. After a 3-hour exposure to 20 micrograms/ml of ARA-C, the cells recovered 38% and 85% of their capacity to synthesize DNA within 4 and 8 hours, respectively. These findings can be explained in part by the short half-life of the intracellular nucleotide pool of ARA-CTP in these cells (about 60 minutes). These data indicate that when there is a prolongation of the interval between exposures to ARA-C, a greater fraction of cells recover from the inhibitory effects of this drug and escape its cytotoxic action. These observations may be important with respect to the design of more optimal schedules of high-dose ARA-C therapy for the treatment of patients with acute leukemia.
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PMID:Effect of the interval between exposures to cytarabine on its cytotoxic action on HL-60 myeloid leukemic cells. 659 37

Resistance of leukemia cells to cytosine arabinoside (ARA-C) may be due to any one or combination of biochemical processes, which in certain instances may be substantially reversed by an appropriate increase in ARA-C dosage. Based on these and other laboratory observations indicating pharmacologic synergy between sequential high-dose ARA-C and asparaginase (HiDAC----ASNase), a therapeutic program was developed for the treatment of patients with acute nonlymphocytic leukemia (ANLL) refractory to conventional doses of ARA-C, as well as patients with high risk ANLL and advanced acute lymphocytic leukemia (ALL). Treatment consisted of 3-hr intravenous infusions of 3 g/sq m of ARA-C given at 12-hr intervals for 4 doses, followed by 6,000 IU/sq m ASNase given i.m. at hour 42. The same schedule was repeated on day 8. In 32 induction attempts, only 4 patients proved to be truly refractory, i.e., failed to achieve substantial leukemia cell cytoreduction. Complete remissions were achieved with HiDAC---- ASNase in 9 of 13 patients with refractory ANLL, 6 of 9 patients with antecedent hematologic disorders, and 3 of 10 patients with advanced ALL. These include 9 of 14 patients who had either failed induction or who had relapsed on active ARA-C therapy and 6 of 8 patients who had had no prior exposure to ARA-C. The median duration of unmaintained remission in ANLL was 5 mo. In a patient with central nervous system (CNS) leukemia, there was clearance of cerebral spinal fluid (CSF) blasts without intrathecal therapy, suggesting a role for HiDAC in CNS prophylaxis. In general, toxicity was tolerable and reversible. These data suggest that HiDAC----ASNase is an exceptionally effective and well tolerated regimen in leukemic patients with antecedent hematologic disorders and in those refractory to conventional doses of ARA-C.
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PMID:Treatment of poor risk acute leukemia with sequential high-dose ARA-C and asparaginase. 669 96

Twenty-seven patients aged from 10 to 60 years (mean 34.4 +/- 13 years) in the first perceptible phase of acute myeloid leukemia were subjected to intensive induction chemotherapy consisting of adriamycin (ADM), vincristin (VCR) and cytosine arabinoside (ARA-C). Twenty-four patients (89%) attained complete remission (CR) after 1 to 3 cycles and were then given an early consolidation treatment with one of the previous cycles. This was followed by long-term continuous maintenance chemotherapy with 6-mercaptopurine (6-MP) and methotrexate (MTX) alternatively and 3-monthly reinforcement courses of donaurubicin (DNR) and VCR. Twenty of these 24 patients were splenectomized soon after the consolidation treatment. None of the spleens were enlarged, and histological sections of the spleens, liver biopsies and mesenteric lymph-nodes stained with routine dyes and by the naphthol AS-D chloroacetate esterase method revealed mature granulocytes but no demonstrable leukaemic cells. In the group of splenectomized patients, the probabilities of staying in complete remission at 27 and 44 months were 70 +/- 12.6% and 52 +/- 18.5% respectively, and the probabilities of remaining alive at 32 and 55 months were 79 +/- 11% and 57 +/- 19% respectively. Age over 40 and evidence of extramedullary infiltration at presentation appeared to leave little hope of disease-free survival. The rationale for the present therapeutic study is discussed.
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PMID:[Treatment of acute myeloid leukemia with a protocol combining intensive induction chemotherapy, early consolidation treatment, splenectomy and long-term maintenance chemotherapy. Preliminary study]. 681 42

An unexpectedly high rate of long-term survivors in acute myeloid leukemia (AML) has been observed in a group of patients who achieved a first complete remission (CR) after induction of a therapeutic regimen including daunorubidomycine, vincristine, prednisone and stanozolol, and anabolizing steroid. The rate of CR was 52%. Maintenance therapy was very simple and the only association with stanozolol during this period suggested to us that an androgen, at low dosages, might be responsible for the unusual long-term survival time (45 months with a 95% confidence limit from 30 to 86 months). On the basis of our first observation, high dosages of the androgen were used during the induction phase of treatment but failed to demonstrate any advantage when associated with a drug regimen, including cytosine arabinoside (ARA-C). The reevaluation of each parameter for our group of patients did not allow selection of patients in terms of their age or the hematologic data obtained at presentation. Effects of androgen on the socalled normal hemopoietic cells and on the leukemic cells are discussed, particularly the possible antagonistic effect with ARA-C. A prospective statement is made concerning the possible condition of the prolongation of the complete remission in AML according to some experimental data which enforce the stimulative activity of androgen on the myeloid proliferation.
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PMID:High rate of long-term survivals in AML treated by chemotherapy and androgenotherapy: a pilot study. 692 14

Three patients with acute myeloid leukaemia were treated with small doses of ARA-C (10 mg/m2/12 h, subcutaneous injections) and complete remission was obtained. The small doses of ARA-C, the progressive evolution, the absence of aplasia before remission, the simultaneous presence of normal islets of promyelocytes and leukaemic myeloblasts, favour a differentiating role for the drug rather than an antimitotic effect.
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PMID:Small doses of ARA-C in the treatment of acute myeloid leukaemia: differentiation of myeloid leukaemia cells? 695 3

Sixty consecutive patients, 15-60 years old, with ANLL were divided randomly into three groups for induction treatment with one of the following regimens: R1, daunorubicin (DNR) 1.5 mg/kg on day 1 + ARA-C 2 mg/kg body weight on days 1-5; R2, DNR 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8; R3, DNR-DNA complex 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8. Maintenance treatment consisted of monthly courses of DNR 1.5 mg/kg (R1, R2) or DNR-DNA 1.5 mg/kg (R3) combined with ARA-C 1 mg/kg on days 1-5, alternating with thioguanine 2 mg/kg PO on days 1-5 combined with ARA-C 1 mg/kg IV on days 1-5. Fourteen patients of 20 went into complete remission with R1, 13 or 18 with R2, and 15 of 22 with R3. The overall remission frequency was 70% and there was no significant difference between the different groups. The median time in first remission and the median survival time were 300 and 510 days, respectively, with R1; 335 and 495 days with R2; and 295 and 677 days with R3. There was no statistically significant difference between the groups treated according to the different regimens concerning the time in first remission. Survival was slightly better with R3 than with R1. Treatment with the DNR-DNA complex caused less pronounced thrombocytopenia and fewer 'minor' cardiac abnormalities than treatment with free DNR in the same dosage schedule.
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PMID:Comparison of daunorubicin and daunorubicin-DNA complex in the treatment of acute nonlymphoblastic leukemia. 702 15

Because of interest in new approaches to treatment of patients with acute promyelocytic leukemia (APL), we analyzed APL treatment outcome in SWOG with chemotherapy from 1982-1991. To evaluate effects of change in nonspecific patient care factors over time we evaluated outcome in two temporal groups (1982-1986, 1986-1991), corresponding to two groups of treatment protocols encompassing all new de novo AML patients entered on acute myeloblastic leukemia (AML) protocols during those years. Surprisingly, APL patients in the 1982-1986 group (n = 45) had much better treatment outcome (complete remission (CR) rate 71%, median overall survival (OS) 106 months, median disease-free survival (DFS) > 105 months) than the later group (n = 96) (CR rate 47%, median OS 13 months, median DFS 28 months) (p = 0.0063, 0.0015, and 0.0001 respectively). All APL patients but two in the 1982-1986 time period were treated on SWOG protocol 8124, which included induction with total daunorubicin (DNR) 210 mg/m2 i.v./course, consolidation with two courses with identical dosage of DNR, and intensification at 4 months including another course of identical dosage DNR. We analyzed factors affecting treatment outcome for all patients with APL treated from 1982 to 1991. In multivariate analysis, higher DNR induction dose was significantly associated with CR rate, OS, and DFS (p < 0.001, < 0.0001, and < 0.0001, respectively). Cytosine arabinoside (ARA-C) dose and inclusion of other agents did not correlate significantly with outcome. Because these studies were not randomized for DNR dosage, other factors contributing to outcome cannot be completely excluded, although none were found. Most deaths occurred within 3 months of initiation of therapy on 8124; there were no relapses with higher DNR dosage after 3 years. This excellent outcome should be considered in evaluating newer modalities of therapy such as all-trans retinoic acid (ATRA) for APL. If the high CR induction rate and minimal early deaths with ATRA therapy can be combined successfully with this chemotherapy, most patients with APL may be curable.
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PMID:Treatment outcome with chemotherapy in acute promyelocytic leukemia: the Southwest Oncology Group (SWOG) experience. 781 35


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