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)

Four cases of hypoplastic leukemia, one of acute myelocytic leukemia (M2) and one of RAEB-t were treated with a low-dose 4N-behenoyl-1-beta-D-arabinofuranosylcytosine (LD-BHAC) regimen, in which 50 mg BHAC was administered daily intravenously by one-hour drip infusion for 14 days. Among the 6 cases, three (2 hypoplastic leukemia and one M2) obtained complete remission and one (hypoplastic leukemia), partial remission. Response rates were 66.6% of all cases, and 75% of cases of hypoplastic leukemia. During treatment, cytopenia was observed in all cases and a decrease in bone marrow nucleated cell counts was recognized in the aged M2 patient with remission. Although side effects of the drug on the digestive system such as anorexia and nausea were observed in some cases, they were all controllable by conventional treatments. The serum concentration of ara-C was measured in 4 cases. The peak level of serum ara-C concentration, 3.62-18.9 ng/ml (mean: 11.74 ng/ml), was observed at the time of cessation of infusion of BHAC, and an ara-C level of 2.75-4.89 ng/ml (mean: 3.54 ng/ml) was still present in the blood 6 hours after the cessation of infusion. It was concluded that LD-BHAC was useful in the clinical management of atypical leukemia and acute myelocytic leukemia in the aged.
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PMID:[Low-dose 4N-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC) in the treatment of atypical leukemia]. 346 49

A 47-year-old female with acute myeloid leukemia received HIV positive platelets during induction chemotherapy. 18 days later, coincident with the recovery of the bone marrow function, she developed an erythematous rash, mild lymphadenopathy, and nausea which disappeared within 10 days. A week later mild CSF pleocytosis consisting of mature lymphocytes and macrophages together with elevated CSF protein levels (1,080 mg/l) were observed suggesting mild aseptic meningitis, and the HIV was concomitantly isolated from CSF. The CSF abnormalities have improved and the patient is well and in remission after 3 cycles of chemotherapy. This case expands the clinical spectrum of HIV infection to include a primary syndrome during immunosuppression from an unrelated cause.
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PMID:Primary infection with HIV in a severely immunosuppressed patient with acute leukemia. 347 78

Aclarubicin is a new anthracycline antibiotic that produces substantially less cardiotoxicity in animals that does doxorubicin. Based upon prior Phase I and II trials in leukemia, a Phase II study in acute myeloblastic leukemia was developed to assess the response rate and toxicity in previously treated patients. Forty patients received aclarubicin 100 mg/m2 per day X 3 with repeated course on days 14-16 if marrow hypoplasia was not produced. Complete responses were achieved in 27.5% (11/40) with durations of 1.5, 2, 2, 2, 3, 3+, 4, 5+, 32+, 33+, and 34+ months. Toxic effects of this therapy included severe neutropenia and thrombocytopenia, nausea/vomiting, mucositis, and diarrhea. No patient developed significant changes in the left ventricular ejection fraction, as measured by radionuclide angiography, or any clinical cardiac symptoms. Alopecia was minimal. Aclarubicin can produce a significant response rate in previously treated patients with acute myeloblastic leukemia and should be considered for study in initial therapy.
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PMID:Phase II study of aclarubicin in acute myeloblastic leukemia. 347 91

Amsacrine and high-dose cytarabine (HiDAc), when administered as single agents, are effective treatment of acute leukemia. When used in combination, a high remission rate is also possible. We treated 47 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic phase of chronic myelogenous leukemia (CML) with a combination of amsacrine and HiDAc. The patients received amsacrine 200 mg/m2 daily for three days and, concurrently, HiDAc 3 g/m2 over three hours once daily for five days. Of 20 evaluable patients with AML in relapse, there were 12 remissions; of seven additional patients with primary refractory AML, there were two remissions, and of 12 patients with ALL in relapse, there were eight remissions. The three patients with blastic phase CML and the three patients with biphenotypic leukemia did not respond. Nausea, vomiting, stomatitis, hepatic dysfunction, and diarrhea were common, but cutaneous, conjunctival, and significant cerebellar and cerebral side effects were absent. We conclude that this regimen is highly effective therapy for AML and ALL and is also safe, eliminating the major toxicities encountered with HiDAc.
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PMID:A new regimen of amsacrine with high-dose cytarabine is safe and effective therapy for acute leukemia. 354 13

Forty-five previously-untreated adult patients with acute myelogenous leukemia (AML) were treated with N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine (BHAC) in a multi-institutional cooperative study. Among 41 evaluable patients, 15 (36.6%) achieved complete remission (CR) and 10 (24.4%) achieved partial remission by daily administration of 3 to 8 mg/kg of BHAC. Higher daily doses (5 mg/kg or more) produced higher CR rates, and all of the CR were observed among the patients receiving a total BHAC dosage of 50 mg/kg or more in a period of 10 days or more. The side effects were mild and acceptable: nausea-anorexia was observed in 27% of the patients and vomiting in 17%. The results of this study thus indicate BHAC to be effective for remission induction of AML, and to deserve further clinical trials in combination with other anti-leukemic drugs.
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PMID:Treatment of acute myelogenous leukemia in adults with N4-behenoyl-1-beta-D-arabinofuranosylcytosine. 386 Dec 33

Aclarubicin, discovered by Umezawa in 1975, is a new cytostatic anthracycline antibiotic. It is one of the anthracyclines with the lowest cardiotoxicity, it is not mutagenic and it stimulates differentiation of tumour cells. The therapeutic index of aclarubicin (efficacy related to toxicity) is higher than that of doxorubicin and daunorubicin, using a proper dose schedule. Single dose therapy of aclarubicin shows only marginal efficacy, whereas multiple divided dose therapy exhibits efficacy comparable to that of doxorubicin and daunorubicin. Thus for clinical trials two dose schedules were designed: 25 mg/m2/day, days 1-7 for acute leukaemia; and 30 mg/m2/day, days 1-4 for solid tumours. Aclarubicin was shown to be highly active in acute leukaemia with 58% complete remissions in first relapse of AML. Good results were also seen in acute leukaemia in combination with cytosine arabinoside and thioguanine. In clinical trials with breast cancer and thyroid cancer the efficacy was in the same range as would be expected for doxorubicin, but side-effects were markedly reduced. Anorexia, mild nausea and infrequent vomiting were observed. Myelosuppression was common but dose reduction was not necessary. There was no alopecia and no congestive heart failure.
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PMID:Aclarubicin: experimental and clinical experience. 391 80

A Phase II clinical trial of NK 171 (Etoposide), a semisynthetic podophyllotoxin, was undertaken in 56 patients with advanced malignant lymphoma and 36 patients with acute leukemia. The dosage of NK 171 was 110-130 mg/m2 day p.o. or 80-100 mg/m2 day i.v. for 5 consecutive days. Of the 92 patients, 23.9% obtained a complete or partial remission. By tumor type, good responses were obtained in non-Hodgkin's lymphoma (34%, 17/50), Hodgkin's disease (25%, 1/4), AML (21.4%, 3/14), and CML-BC (25%, 1/4). Side effects included leukopenia (78.4%), alopecia (62.0%), anorexia (40.2%), nausea (30.4%) thrombocytopenia (25.6%) and fever (16.3%). These results demonstrated NK 171 to be an effective agent against malignant lymphoma and acute myeloblastic leukemia.
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PMID:[Phase II study of NK 171 (etoposide) on malignant lymphomas and acute leukemia. A cooperative study group on NK 171 in hematological malignancies]. 395 73

Etoposide (VP 16) is a semi-synthetic derivative of 4'- demethylepipodophyllotoxin , a naturally occurring compound synthesized by the North American May apple (Podophyllum peltatum ) and the Indian species Podophyllum emodi Wallich . Although podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking mitrotubular assembly, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), probably via inhibition of DNA synthesis. There appears to be a selective antileukemic dose response relationship when compared to normal hematopoietic elements. Etoposide is effective when administered orally at about twice the recommended parenteral dosage. Schedule dependency in both animal models and clinical trials has been observed; multiple dosing over three to five consecutive days is superior to weekly single dose administration. Etoposide's dose-limiting toxicity is myelosuppression (leukopenia), which is quite predictable; alopecia and Gl toxicity (nausea, vomiting, stomatitis) occur in about 20-30% of patients given recommended dosages. Etoposide appears to be one of the most active drugs for small cell lung cancer, testicular carcinoma (the Food and Drug Administration approved indication), ANLL and malignant lymphoma. Etoposide also has demonstrated activity in refractory pediatric neoplasms, hepatocellular, esophageal, gastric and prostatic carcinoma, ovarian cancer, chronic and acute leukemias and non-small cell lung cancer, although additional single and combination drug studies are needed to substantiate these data. Its contribution in front-line combination chemotherapeutic regimens for these cancers will be better defined in the forthcoming years. Etoposide appears to have minimal activity in breast cancer and, based on current data, it is inactive against malignant melanoma, colorectal adenocarcinoma and cancer of the head and neck, although the dosage and schedules used in many of the Phase II studies may have been suboptimal.
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PMID:Etoposide: a semisynthetic epipodophyllotoxin. Chemistry, pharmacology, pharmacokinetics, adverse effects and use as an antineoplastic agent. 632 63

The toxic effects of high-dose busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) with autologous or syngeneic bone marrow rescue were evaluated in 19 patients (11 with acute myelocytic leukemia, one with acute lymphocytic leukemia, one with acute myelofibrosis, two with chronic myelocytic leukemia, one with Hodgkin's disease, and three with non-Hodgkin's lymphoma). Their mean age was 26 years (range, 6-50); nine patients had syngeneic and ten had autologous bone marrow rescue (six of whom had in vitro bone marrow incubation with 4-hydroperoxycyclophosphamide). Severe myelosuppression was expected and was seen in all patients; leukocyte and platelet count recovery occurred at a median of 19 days (range, 11-59) and 30 days (range, 20-89), respectively. Nausea, vomiting, and diarrhea were frequent but readily managed with vigorous medical therapy. Stomatitis was severe in 14 patients. Skin, renal, cardiac, pulmonary, and CNS complications directly attributable to drug-related toxic effects were transient and non-life-threatening. Hepatic function abnormalities were common but tended to be transient. Most patients tolerated high-dose busulfan and cyclophosphamide with manageable side effects. Hepatic veno-occlusive disease was fatal in two patients, while diffuse interstitial pneumonitis with disseminated herpes virus infection was fatal in three patients with lymphoma. All patients treated in relapse or without previous therapy had a complete tumor response. Further studies with this regimen should be pursued.
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PMID:Preliminary results of high-dose busulfan and cyclophosphamide with syngeneic or autologous bone marrow rescue. 637 4

Twelve patients with refractory acute leukemia (7 patients with acute myelocytic leukemia and 5 patients with acute lymphocytic leukemia) were treated with a new anthracycline antibiotic, aclacinomycin-A (ACM). ACM was administrated by intravenous drip infusion at a dose of 20 mg/day for 7 or 14 days and this was repeated after at least 7 days. Four of 12 patients (33.3%) achieved a complete remission; 3 of 7 acute myelocytic leukemia (42.8%) and 1 of 5 acute lymphocytic leukemia (20.0%). The days required for achieving the complete remission ranged from 23 to 78 days (median: 61) and the total doses of ACM used from 180 to 500 mg (median: 310), and the durations of complete remission from 11 to 28+ weeks (median: 21+). The untoward effects on digestive organs, such as nausea, vomiting and anorexia, and hematological toxicities were frequently seen; however, they were controlled by supportive treatment. Alopecia was not observed. Arrythmia was recognized in one patient at the initiation of ACM infusion with complete remission without withdrawal of ACM. These results suggest that ACM is a potentially effective anthracycline antibiotic in the clinical management of acute leukemia.
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PMID:Treatment of refractory acute leukemia with aclacinomycin-A. 644 34


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