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)

52 patients with refractory or relapsed acute myeloid leukaemia (AML) were randomly assigned to receive a combination of high-dose cytosine arabinoside (HD Ara-C), 3 g/m2/d and either mitoxantrone (MTX), 7 mg/m2/d (5 mg if older than 60 yr) or m-amsacrine (AMSA), 120 mg/m2/d (90 mg if older than 60 yr) for 5 d. The overall response rate was 50% and did not differ significantly in the two groups (46% for AMSA and 56% for MTX, p = 0.415). The median survival was 11 months (8 months for AMSA and 12 months for MTX, p = 0.326) and the median duration of complete remission (CR) was 11 months for AMSA and 12 months for MTX (p = 0.643). In relapsed patients, the only significant predictive factor for obtaining a complete response was the length of first complete remission. Patients with a first CR shorter than 6 months had a CR rate of 36% while it was 65% if the first CR lasted more than 6 months (p = 0.03). Severe (WHO grade III-IV) gastro-intestinal toxicity was more frequent in the AMSA group (27% vs 4%, p = 0.021). Treatment-related death occurred in 4 patients in the AMSA group and in 2 patients in the MTX group (p = 0.097). We conclude that neither of these two treatment modalities was shown to be superior in terms of CR rate and survival, with a better tolerance for MTX.
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PMID:High-dose cytosine arabinoside and amsacrine or mitoxantrone in relapsed and refractory acute myeloid leukaemia: a prospective randomized study. 222 29

We previously administered ara-C at a dose rate of 250 mg/m2/hr for 36-72 hr to patients with leukemia. Gastrointestinal toxicity was dose-limiting. This regimen was modified to an every other day schedule, administering 24-hr periods of high dose continuous infusion ara-C, each followed by a 24-hr rest period. Sixteen patients with relapsed/refractory acute myeloid leukemia (AML) (N = 4), secondary AML (N = 2), relapsed/refractory acute lymphoblastic leukemia (N = 7), or CML in blast crisis (N = 3) received this regimen of three 24-hr infusions with two intercurrent 24-hr rest periods. Grade 3 gastrointestinal toxicity was encountered in 57% of the courses, and hypoplasia was achieved in all patients. Three of the patients died while hypoplastic, two with septicemia and another with intracranial hemorrhage. There were five responding patients (2 CRs, 3 PRs). Median steady-state plasma ara-C levels were 24 microM, 22 microM, and 20 microM during the first, second, and third 24-hr infusions, respectively. Ara-C levels ranged from 4-118 microM during the infusions and were always below 4.5 microM during the rest periods. A significant level of ara-C incorporation into DNA was detected in each of the five patients studied, thus demonstrating that (ara-C)DNA formation is detectable in blasts from patients receiving high dose continuous infusion ara-C therapy. These findings suggest that alternate day continuous infusion ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.
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PMID:A phase I study of intermittent continuous infusion high dose cytosine arabinoside for acute leukemia. 224 7

In a single centre, 52 newly diagnosed patients with acute myeloid leukemia (AML) under the age of 56 years received induction chemotherapy commencing with high-dose cytosine arabinoside (Ara-C) and etoposide (Protocol BF11), followed by Ara-C, 6 thioguanine (6TG). A total of 67% of patients entered remission using these drugs. An anthracycline was added for those patients not in remission. The overall remission rate (CR) was 86.5% (45/52), with a minimum follow-up of 90 days. Patients are hospitalised for relatively short periods, and consequently require less blood product and antibiotic support. Patients in continuing first remission following induction with Ara-C and etoposide are similar in number to those in continuing first remission who initially received an anthracycline. This would imply that the efficiency of Ara-C and etoposide in inducing long-term disease-term survival is comparable with anthracycline-containing regimens. We conclude that high-dose Ara-C and etoposide used in the first induction cycle for treating AML have good antileukaemic effect with acceptable toxicity.
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PMID:High-dose cytosine arabinoside plus etoposide as initial treatment for acute myeloid leukaemia: a single centre study. 224 76

A 36-year-old man with acute myelogenous leukemia, refractory to the combination chemotherapy, developed fungal infection and acute respiratory distress. Simultaneously, rapid proliferation of leukemic cells was observed in the blood. He was given continuous drip infusion of etoposide (50 mg/day) and Ara-C (20 mg/day) for 18 days. The leukemic cells disappeared from both the blood and the marrow, and complete remission was achieved. There was no adverse effect related to this therapy. The low dose combination chemotherapy with etoposide and Ara-C is safe to be carried out, and could be effective for the patients with refractory leukemia.
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PMID:[Low dose continuous infusion therapy with etoposide (VP-16) and cytosine arabinoside (Ara-C) for a patient with refractory acute myelogenous leukemia]. 228 79

In this study 10 patients with acute myelocytic leukemia (AML) each received a rapid intravenous injection of high dose cytosine arabinoside (HD Ara-C; 1 g/m2). Bone marrow aspirates were obtained before and after Ara-C administration to determine the percentage of cells in S-phase measured by flow cytometry. In 5 out of 10 cases synchronization of the leukemic cells in S-phase of the cell cycle was observed. However, the time of maximum synchronization turned out to be difficult to predict. Therefore, the strong correlation between percentage of cells in S-phase at diagnosis and the time of maximal accumulation of S-phase cells after Ara-C administration, as observed by others in childhood AML, could not be confirmed for adult AML patients. Although synchronization of AML cells after in vivo Ara-C administration could be demonstrated in at least half of the patients, the practical consequences are such that clinical application was hampered.
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PMID:Cell kinetics after high dose cytosine arabinoside in patients with acute myelocytic leukemia. 230 66

Differentiation induction therapy provides an alternative for treatment of patients with acute myeloid leukaemia (AML) who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid (RA) + low concentration of cytarabine (Ara-C) + dimethylformamide (DMF) on the differentiation of blasts from 24 AML patients was studied. Nonadherent mononuclear cells were cultured at a concentration of 5 x 10(5) cells/ml in 24-well tissue culture plates containing RPMI 1640 culture medium with 20% fetal calf serum, 10% autologous serum and 10% 5637-conditioned medium and incubated with 10(-6) M RA, 10(-6) M Ara-C and/or 100 mM DMF alone and in combination with each other for 6 days in primary culture at 37 degrees C in a humidified incubator under 5% CO2. The triple combination of 10(-6) M RA + 10(-6) M Ara-C + 100 mM DMF induced 90% of blasts from 22 out of 24 AML patients to differentiate. These highly effective results justify a clinical trial of this triple combination for AML patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy.
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PMID:Triple combination of retinoic acid, low concentration of cytarabine and dimethylformamide induces differentiation of human acute myeloid leukaemic blasts. 230 25

Seven patients with acute myeloid leukemia (AML) in first complete remission were treated with escalating high doses of cyclophosphamide, etoposide, and cytosine arabinoside (Ara-C). In all patients autologous bone marrow preservation was performed prior to therapy. Bone marrow was stored in blood bags in a refrigerator for 48-72 h at 4 degrees C and then reinfused over a central line. All patients had a full hematological recovery. The mean time of neutropenia (neutrophils less than 500/microliters) was 14 days (range 9-24 days), and the mean time of thrombocytopenia (platelets less than 20,000/microliters) was 9 days (range 7-11 days). The nonhematological toxicity was tolerable with mild to moderate nausea/vomiting, mucositis and diarrhea, and so far not dose-limiting. Six patients remain in complete remission 17+, 9+, 5+, 5+, 4+, and 1+ months after autotransplantation. One patient relapsed 8 months after autotransplantation. High-dose chemotherapy with noncryopreserved bone marrow autotransplantation may be useful as intensified consolidation for patients with AML in first complete remission.
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PMID:High-dose chemotherapy with noncryopreserved autologous bone marrow transplantation for acute myeloid leukemia in first complete remission. 232 69

A 16 year-old boy was admitted to our hospital in April 1985, because of bilateral submandibular swellings. Hematological examination revealed Hb was 7.3 g/dl, WBC was 89,000/microliters (76% blast), and platelet was 154,000/microliters. His bone marrow was hypercellular and consisted with 91% blasts. Myeloperoxidase staining was positive for 38% of blasts. Auer rods were seen in some of blasts. Thus, the diagnosis was M1 according to FAB classification. Cytogenetic studies of 20 marrow cells were performed and all cells had 46, XY, -1, -7, 3q-, 7q-, 17q+, +2mar. Eighty five percent of blasts expressed HLA-DR and 43% of blasts expressed CD2 and CD13 simultaneously. Thus, this leukemia was considered as the hybrid type of acute mixed leukemia by surface marker analysis. DBMP-85 regimen, the chemotherapy for AML, was started after admission and complete remission (CR) was attained in June 1985. After 4 courses of post remission chemotherapy, he discharged in December 1985 and was followed at our outpatient clinic without chemotherapy. His disease was relapsed in June 1986, and the combination chemotherapy with mitoxantrone, etoposide and Ara-C was applied to him but failed to attain CR. Then, LVP protocol, the chemotherapy for ALL, was started and CR was achieved. The blasts at relapse had morphologically myeloid features, and expressed HLA-DR, CD2 and CD13 as well as at diagnosis. Cytogenetic studies at relapse showed some karyotype except gaining 12p- anomaly. Therefore, same blasts were considered to emerge at relapse. Our case suggests that LVP therapy may be effective for AML expressing myeloid and lymphoid surface markers.
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PMID:[DBMP-85 was effective at diagnosis and LVP was effective at relapse in a case of acute mixed leukemia]. 236 35

Schedule-dependent interaction of 1-beta-D-arabinofuranosylcytosine (ara-C, cytarabine) plus doxorubicin or ara-C plus mitoxantrone was studied in vitro using HL-60 human acute myelocytic leukemia cell line. The cells were exposed for 1 hr to each drug simultaneously, or sequentially (up to a 28-hr interval), and cell kill effects were determined by clonogenic assay. The results were compared with controls in which cells were exposed to the individual drug only and seeded after appropriate intervals. Simultaneous exposure to two drugs produced lethal effects, but no more than those produced by doxorubicin or mitoxantrone alone. Ara-C followed by doxorubicin produced time-dependent increases in cell kill that was parallel to the doxorubicin alone control, indicative of no true potentiation. In contrast, ara-C followed by mitoxantrone produced striking increases in cell kill effects. Thus, ara-C followed by mitoxantrone resulted in more than 10-fold increases in cell kill at the intervals of greater than or equal to 8 hr between exposures, and the strong cell kill effects were maintained. Our data indicate that: (a) simultaneous exposure to ara-C and doxorubicin or mitoxantrone is less than additive; (b) ara-C followed by doxorubicin is probably only additive; and (c) ara-C followed by mitoxantrone is more than additive, and cell kill effects are sustained.
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PMID:Schedule-dependent interaction of cytarabine plus doxorubicin or cytarabine plus mitoxantrone in acute myelocytic leukemia cells in culture. 238 78

Thirty-nine patients with acute myeloblastic leukemia (AML) in first complete remission (CR) were treated by autologous bone marrow transplantation. All patients received the same induction and consolidation chemotherapy consisting of a combination of daunorubicin (DNR) and cytarabine (Ara-C) followed by four courses of DNR, Ara-C and 6-thioguanine (6-TG). Two different conditioning regimens were used; 25 patients were submitted to the BAVC regimen (BCNU, amsacrine, VP-16 (etoposide) and Ara-C) and 14 to a cyclophosphamide/total body irradiation (CY + TBI) regimen. Six patients (one treated with BAVC and five treated with CY + TBI) died in aplasia. Twelve of the 25 BAVC treated patients and one of the nine CY + TBI treated patients relapsed; 12 (48%) of the BAVC treated patients are in CR with a median follow-up of 45 months and eight (57%) of the CY + TBI treated patients are in CR with a median follow-up of 50 months. All patients in CR have survived for more than 2 years since transplant.
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PMID:Autologous bone marrow transplantation in patients with AML in first complete remission. Results of two different conditioning regimens after the same induction and consolidation therapy. 240 28


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