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)

A 76-year-old woman, who had suffered from liver cirrhosis, was referred to our hospital because of pancytopenia. Her peripheral leukocyte count was 2,500/microliters with 43% myeloblasts, hemoglobin at 9.0 g/dl and platelet count of 0.9 x 10(4)/microliters. Aspirate from bone marrow showed hypercellular marrow with 52% myeloblasts. No chromosomal abnormality was detected. She was diagnosed as acute myelogenous leukemia (AML, M2). The diagnosis of liver cirrhosis was confirmed by laboratory data and findings of abdominal sonography. Moreover, she had valvular aortic stenosis. These complications made it difficult to treat her with combined chemotherapy containing anthracycline antibiotics, so she was given a small dose of cytosine arabinoside (Ara-C, 10 mg/body/12 hr) for 18 days. After severe myelosuppression, complete remission was achieved. The highest serum concentration of Ara-C was obtained at 15 min after subcutaneous injection of Ara-C; thereafter the Ara-C concentration decreased immediately within 60 min in a pattern similar to that observed in patients without liver cirrhosis. Thus, low-dose Ara-C regimen might be a useful treatment for aged patients with AML, even complicated with liver cirrhosis.
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PMID:[An aged patient with acute myelogenous leukemia complicated with liver cirrhosis: successful treatment with low-dose cytosine arabinoside]. 275 21

In an effort to increase the proportion of patients with acute myeloid leukemia (AML) remaining in continued complete remission (CCR), we administered intensive postremission consolidation therapy with high-dose cytarabine (Ara-C) and daunorubicin. Eighty-seven patients, with a median age of 38 years (range, 7 to 71), received consolidation therapy after first complete remission was obtained with standard induction chemotherapy that included conventional doses of Ara-C. Consolidation therapy consisted of from one to three cycles of high-dose Ara-C (3 g/m2 intravenously [IV] over 1 hour every 12 hours for 12 doses) followed by daunorubicin (30 mg/m2/d IV bolus for 3 days). After completion of the high-dose Ara-C and daunorubicin, no further therapy was administered. Myelosuppression encountered with consolidation resulted in a median duration of neutropenia and thrombocytopenia of 3 weeks. Four patients (5%) died during consolidation due to infection and/or hemorrhage; 59% of patients experienced severe but nonfatal infectious or extramedullary organ toxicity. With a median follow-up of more than 3.5 years from diagnosis, the proportion of patients, by Kaplan-Meier product-limit estimate, remaining in CCR is 49% (95% confidence limits, 37% to 61%). In a Cox multivariate analysis, only age significantly (P less than .001) influenced the probability of remaining in CCR. The probability of remaining in CCR was 83%, 50%, and 23% for age groups of 25 or less, 26 to 45, and more than 45 years, respectively. These survival curves all have stable long-term plateaus, suggesting cure. In this study, the administration of brief, intensive nonmarrow ablative chemotherapy resulted in a large proportion of patients with AML remaining in CCR, results similar to those reported with allogeneic bone marrow transplantation. Relapse of acute leukemia was still the major reason for therapy failure, suggesting that more effective or additional postremission therapy will be required to further improve the likelihood of cure especially for older patients.
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PMID:High-dose cytarabine and daunorubicin as consolidation therapy for acute myeloid leukemia in first remission: long-term follow-up and results. 236 Sep 32

Forty-seven patients with primary refractory, relapsed, and previously untreated, poor risk AML were entered into a phase II study of intermediate dose ARA-C (IDAC) (1 g/m2 i.v. over 6 hr, daily for 6 days) with sequential mitoxantrone (MITOX) (6 mg/m2 i.v. bolus 3 hr after the end of each ARA-C infusion). Overall, complete remission was induced in 31 patients (66%), and 1 additional patient entered a partial remission. Seven patients (15%) died of infection during marrow hypoplasia. Response to IDAC + MITOX was influenced by sensitivity to previous therapy: patients with primary refractory and early relapse AML responded less well to the regimen (CR rate 28% and 33%, respectively), as compared to those with previously untreated (CR rate 64%) or late relapse disease (CR rate 85%). Sixteen patients continue in CR at 1-12+ months. Except for the expected severe myelosuppression, the regimen was well tolerated with minimal extramedullary toxicity. The data indicate that the sequential combination of IDAC and MITOX is an effective and tolerable regimen for AML. Consideration should be given to applying this program at earlier stages of AML therapy.
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PMID:Phase II trial of intermediate dose ARA-C (IDAC) with sequential mitoxantrone (MITOX) in acute myelogenous leukemia. 291 Dec 4

Thirty-one patients with a diagnosis of refractory acute myelogenous leukemia received homoharringtonine as their first (15 patients) or second (16 patients) salvage therapy. Homoharringtonine was given as a continuous infusion of 2.5 mg/m2 daily for 15 to 21 days to 13 patients (schedule 1), and of 3.0 mg/m2 daily for 15 days in 18 patients (schedule 2). Overall, one patient achieved complete remission (3%), and three (10%) had a hematologic improvement with normalization of the marrow and peripheral blood picture except for persistent thrombocytopenia. Six patients (19%) demonstrated prolonged myelosuppression, three (23%) on schedule 1 and three (17%) on schedule 2. Cardiovascular complications were minimal consisting of hypotension in one patient (3%) and supraventricular arrhythmias in two patients (6%). Hyperglycemia was observed in 42% of patients and was significant in 10%. The authors conclude that homoharringtonine, at the dose schedule investigated, has definite but low antileukemic efficacy. The low-dose continuous infusion schedule was associated with prolonged myelosuppression but no serious cardiovascular complications. The role of such therapy in myeloproliferative disorders, especially chronic myelogenous leukemia, deserves consideration.
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PMID:Phase II study of low-dose continuous infusion homoharringtonine in refractory acute myelogenous leukemia. 291 87

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and adverse effects of mitoxantrone are reviewed. Mitoxantrone, an aminoanthraquinone that was synthesized in 1979, belongs to a new chemical class of agents known as the anthracenediones. It possesses antiviral, antibacterial, immunomodulatory, and antitumor activity. The drug's antitumor activity is attributed to its interaction with DNA topoisomerase II, and its interaction with human cells may also involve nonintercalary, electrostatic interactions. Mitoxantrone is poorly absorbed orally and is most commonly administered intravenously. The drug is rapidly distributed into the red blood cells, white blood cells, and platelets, followed by deep-tissue sequestration. Mitoxantrone has demonstrated clinical efficacy in the treatment of leukemia, lymphoma, and breast cancer. As a single agent, mitoxantrone has a response rate of roughly 30% in acute nonlymphocytic leukemia or acute myeloid leukemia. In combination with other standard agents (cytarabine, vincristine, and prednisone), the response rate may reach 60%. In breast cancer, mitoxantrone's response rate as a single agent is 25-30%, while combination regimens produce response rates of 60% or more. The drug can cause cardiotoxicity with cumulative doses. Other adverse effects include myelosuppression, nausea and vomiting, stomatitis, mucositis, and alopecia. The cost of mitoxantrone is comparable to that of doxorubicin, but it is substantially more expensive than daunorubicin. Mitoxantrone is an important new agent with antitumor activity in leukemia, lymphoma, and breast cancer. In most situations, mitoxantrone will be considered second-line treatment or a restricted-use item because of its high cost and because of the lack of FDA approval for indications other than acute nonlymphocytic leukemia.
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PMID:Mitoxantrone: a novel anthracycline derivative. 304 48

The ability to transplant bone marrow makes it possible to treat patients with hematologic malignancies with doses of systemic radiotherapy or chemotherapy that would ordinarily result in fatal myelosuppression. With this approach, some otherwise incurable patients can be treated successfully. For most hematologic malignancies (acute nonlymphocytic leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and malignant lymphoma), if transplantation is delayed until patients have end-stage disease (drug-resistant relapse) or blast crisis, approximately 10 to 20% of patients can be saved. If transplantation is carried out earlier in the course of disease, the outcome improves considerably. Some of the major limitations of marrow transplantation are the need for an appropriate source of marrow, the severe myelosuppression seen in the immediate posttransplant period, the complications of graft-v-host disease (GVHD), and disease recurrence. The use of autologous marrow and the formation of a national donor registry may make transplantation more widely applicable. The availability of growth factors can hasten hematopoietic recovery, making the immediate posttransplant period safer. New immunosuppressive regimens and T-cell depletion of donor marrow can diminish the impact of GVHD. The need for better preparative regimens persists and has emerged as the major requirement for continued progress in marrow transplantation.
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PMID:Marrow transplantation for hematologic malignancies: a brief review of current status and future prospects. 305 5

High dose cytarabine (HDARAC) therapy is used increasingly to treat hematologic malignancies. Recent data indicate that HDARAC at doses of 2-3 g/M2 every 12 hr x 10-12 doses is of comparable or greater efficacy in remission induction as standard doses of cytarabine in acute myelogenous leukemia. HDARAC can also produce remissions in individuals resistant to conventional doses. HDARAC-containing regimens are reported to result in substantially higher long-term, disease-free survival than previous approaches to post-remission therapy, but this has not yet been confirmed in controlled trials. HDARAC is also active in acute lymphocytic leukemia. Because intravenous HDARAC achieves high levels in the spinal fluid, it is useful to treat central nervous system leukemia and may provide adequate CNS prophylaxis in acute lymphocytic leukemia. HDARAC is reported to be active in advanced non-Hodgkin lymphomas and chronic myelogenous leukemia in acute phase; optimal use in these settings is under study. HDARAC has also been combined with other drugs. Randomized trials are needed to determine whether these combinations are more effective than HDARAC alone. Apart from potent myelosuppression, the dose-limiting toxicity of HDARAC is cerebellar damage. This occurs with increased frequency in patients greater than 50 years old. HDARAC is active in hematologic malignancies and may further improve therapeutic results if combined with other drugs.
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PMID:High dose cytarabine: a review. 328 15

High doses of cytosine arabinoside (ara-C) were administered by continuous infusion to 24 patients with acute leukemia in relapse or blast phase of chronic myelogenous leukemia (CML). Ara-C was infused at a dose rate of 250 mg/M2/hr for 36 to 72 hr. The major toxicities were myelosuppression, diarrhea, and abdominal pain. Other toxicities included pulmonary edema, neurotoxicity, and liver function abnormalities. The gastrointestinal toxicity was dose-limiting and a phase II dose was established at 250 mg/M2/hr for 60-72 hr. Four patients treated with this dose schedule had objective responses. Two patients with CML in blast phase returned to chronic phase and have remained stable without maintenance therapy for 12 and 18 months. Two patients with acute myelogenous leukemia in relapse entered complete remissions which continued unmaintained for 4 and 6 months. Steady-state plasma ara-C levels ranged between 7 and 24 x 10(-6) M, while ara-U levels were as high as 4.5 x 10(-4) M. There was no detectable accumulation of ara-C or ara-U during the infusion period. These findings would suggest that the continuous infusion of high dose ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.
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PMID:Prolonged high dose ARA-C infusions in acute leukemia. 328 17

Eighty-four previously treated adult patients with acute leukemia and malignant lymphoma were treated with (2"R)-4'-O-tetrahydropyranyladriamycin (THP). THP (10-55 mg/m2) was administered by i.v. bolus injection daily for acute leukemia, and according to three different schedules for malignant lymphoma: daily, weekly or once every 3-4 weeks. Complete and partial remission (CR and PR) were achieved by 1 (5%) and 3 of 19 patients with acute myelogenous leukemia and by 2 (13%) and 3 of 15 patients with acute lymphoblastic leukemia, respectively. All CRs were in the groups receiving 25 mg/m2 THP daily. CR and PR were achieved by 6 (14%) and 8 of 42 patients with non-Hodgkin lymphoma (NHL) and by 4 (50%) and 2 of 8 patients with Hodgkin's disease (HD), respectively. No particular sensitivity was found among the subtypes of NHL and HD. Response (CR + PR) was noted in 10 (40%) of 25 patients treated every 3-4 weeks, in 1 (17%) of 6 treated weekly, and in 9 (47%) of 19 treated daily. The major side effects were myelosuppression and gastrointestinal toxicities. Alopecia was observed in only 10 (12%) patients. ECG abnormalities were observed in 7 (10%) patients, all of whom had previously been treated with other anthracyclines. No severe cardiotoxicity was observed.
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PMID:Treatment of acute leukemia and malignant lymphoma with (2"R)-4'-O-tetrahydropyranyladriamycin. 331 82

Seventeen patients with relapsed or refractory acute nonlymphocytic leukemia were treated with 14 mg/m2 of mitoxantrone given in a 30-minute infusion daily for three days. If the day fourteen bone marrow showed residual leukemia, a second course was given at the same dose for two days. Eight patients (47%) entered complete remission. Three patients (17%) had a partial response, four (24%) did not respond, and two (12%) died with hypoplastic marrows during treatment. Seven of the 12 relapsed patients entered a complete remission, as did one of the five refractory patients. Toxicity was acceptable; prolonged myelosuppression, moderate hepatic toxicity, and stomatitis were the only problems. Several dose schedules of mitoxantrone have been studied by other investigators with varying results. The three-day schedule in the present study is similar to the schedule used for common induction regimens employing anthracycline drugs. On the basis of its activity and acceptable toxicity in relapsed and refractory ANLL patients, we feel that this schedule could be safely combined with other agents in future studies.
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PMID:Mitoxantrone in relapsed or refractory acute nonlymphocytic leukemia. 338 61


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