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 65-year-old white male with acute myelogenous leukemia received whole brain irradiation (2550 rads) and intrathecal cytosine arabinoside for CNS prophylaxis. Bone marrow remission had been previously achieved with systemic chemotherapy (vincristine, Adriamycin, prednisone, and cytosine arabinoside). Two weeks following the last intrathecal cytosine arabinoside treatment, the patient developed a spastic paraparesis requiring the use of a walker. A gas myelogram was normal and CSF examination revealed a protein of 50 mg/100 ml but was otherwise unremarkable. Five months later, the patient had improved in that he could stand on his own. A relapse of his leukemia subsequently occurred and the patient died the following month. Striking degenerative changes were found in the spinal cord at postmortem examination. These included microvacuolization, axonal swellings, and loss of myelin with scattered macrophages laden with fat.
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PMID:Paraparesis following intrathecal cytosine arabinoside: a case report with neuropathologic findings. 27 Oct 37

Adriamycin (ADR)-induced cardiomyopathy was studied in a rat model by means of electrocardiograms (ECGs), light microscopy, and determination of heart weight. Pretreatment with D-alpha-tocopherol (alpha-T) 24 hours prior to a high dose of ADR diminishes cardiotoxic effects, as judged by ECG changes, decreases in heart weight, and histologic changes. The response of an acute myeloid leukemia in a rat model to ADR was not affected by this pretreatment. The results provide evidence that alpha-T might be used to improve the therapeutic index of ADR.
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PMID:Effect of alpha-tocopherol on the cardiotoxicity of adriamycin in the rat. 27 40

One hundred and thirty-three patients, 94 with acute luekemia and 39 with solid tumors, received rubidazone, alone or in combination, at M. D. Anderson Hospital. The initial study, a phase I--II study carried out in 39 patients with acute leukemia, revealed substantial antileukemic activity with optimal results at a dose level of 450 mg/m2. Toxic manifestations included an acute reaction suggestive of histamine release with dose-limiting mucositis at a dose of 600 mg/m2. Forty-seven patients with acute leukemia were treated at phase II dose levels. Thirteen of 32 patients (42%) with acute myelogenous leukemia and seven of ten patients (70%) with acute lymphocytic leukemia achieved complete remission. Twenty-seven previously untreated patients with acute leukemia who were greater than 50 years old were treated with rubidazone in combination with cytosine arabinoside, vincristine, and prednisone. Fifteen patients (50%) achieved complete remission including 12 of 15 patients (73%) who were treated at a dose of 200 mg/m2 of rubidazone on Day 1 and a dose of 70 mg/m2/day X 7 days of cytosine arabinoside (continuous infusion). For patients with solid tumors, the dose-limiting toxic effect was myelosuppression at a dose of 200 mg/m2. Other toxicity at that dose level was minimal. The best responses were seen in patients with carcinoma of the period with two of four evaluable patients showing objective tumor regression. Of six previously untreated patients with thyroid carcinoma none responded, and in a phase II study of patients with breast cancer there were no partial remissions among 13 patients. Cardiac toxicity, manifested by congestive heart failure, occurred in seven patients at cumulative doses of 1050--2600 mg/m2 of rubidazone; all patients had had prior anthracycline therapy at low doses. Rubidazone has been shown to be an active antileukemic agent, but appears to be less active than Adriamycin in our studies of patients with solid tumors.
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PMID:Clinical studies with rubidazone. 28 57

In an attempt to improve remissions and survivals in previously treated patients with adult acute leukemia, we gave Adriamycin, vincristine, and prednisone for induction therapy, followed by 6-mercaptopurine and methotrexate for maintenance therapy to patients attaining complete remission (CR). The study group consisted of 18 patients with acute myeloblastic leukemia (AML), ten with acute lymphoblastic leukemia, and one with acute undifferentiated leukemia. Only one patient had previously received Adriamycin. Overall, there were ten CRs and two partial remissions. The five CRs and one partial remission in patients with AML occurred among those with one prior induction attempt; none of the eight AML patients with more than one prior induction attempt responded. The actuarial median duration of CR was 15 weeks and was similar for AML and acute lymphoblastic leukemia patients. Responders had a longer median survival (30 weeks) than nonresponders (9 weeks). Thus, although a reasonable number of responses in previously treated patients were obtained with this program, improvements in maintenance therapy are clearly needed.
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PMID:Reinduction therapy for adult acute leukemia with adriamycin, vincristine, and prednisone: a Southwest Oncology Group study. 28 42

Adriamycin is now firmly established as a drug with a very broad spectrum of antitumor activity. It has had a major impact on the therapy of sarcomas. The dose response effect in this tumor is steep and combinations which compromise the dose of adriamycin too greatly are showing inferior results. In lung and breast cancer combinations with adriamycin have been extensively tried. The FAC Regimen in breast cancer has given excellent results at the M.D. Anderson Hospital. The inclusion of adriamycin in combinations has had an impact in the poor prognosis histologies of non-Hodgkin's lymphomas. The CHOP regimen is one of the best developed to date for diffuse histiocytic lymphomas. In the leukemias adriamycin is probably equivalent to daunorubicin which has been more extensively used in this country. A new analog called Rubidazone has shown good activity in AML with a smooth induction and its incorporation into combination with Ara-C, vincristine and prednisone in a regimen called ROAP is being investigated. Adriamycin in complex with DNA has been clinically evaluated, but at this time, no advantage for this approach can be demonstrated.
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PMID:Adriamycin and other anthracycline antibiotics under study in the United States. 36 Mar 30

Forty-six previously untreated patients with acute nonlymphocytic leukemia were treated with a remission induction regimen consisting of three daily doses of Adriamycin (30 mg/m2/day) and a ten-day continuous infusion of cytosine arabinoside (ara C) (100 mg/m2/day). The overall remission rate was 72%, with 88% of the patients less than 50 and 62% of patients greater than 50 years old achieving complete remission status. Thirty-one of the 33 complete remissions occurred after a single course of chemotherapy. Retrospective comparison of this regimen with its predecessor (identical, except that a seven-day infusion of ara C was administered) demonstrated that the increase in duration of ara C administration resulted in greater antileukemic effectiveness without an increase in hematologic toxicity to the patient.
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PMID:Remission induction in acute nonlymphocytic leukemia: comparison of a seven-day and ten-day infusion of cytosine arabinoside in combination with adriamycin. 54 91

Anthracyclines, such as daunorubicin (DNR), rubidazone (RBD) and adriamycin (ADR) are intercalating drugs used in cancer chemotherapy. They inhibit synthesis of DNA and RNA, break DNA and inhibit mitochondrial oxidative chain. Their antitumoral experimental activities depend upon type of drug, tumor and route of administration. After i.v. administration, the drug is present in all tissues except central nervous system. Its disappearance from the plasma is biphasic with a long terminal half life, justifying intermittent chemotherapy. Anthracyclines metabolism occurs mainly in liver micrososomes, and 90% metabolites are excreted in the bile. The main toxicity is cardiac, as a congestive heart failure which appears when a cumulated drug dose is overcome. In man only, a few derivatives have been studied, compounds with activity and no cardiotoxicity are still in research. Action of malignancies depends on type of derivative. We use DNR since 1967, it is a remarkable active drug in induction treatment of AML, it is the only active drug on acute promyelocytic leukemia, and it increases number of remissions in all of adult patients and severe forms of children ALL. Adriamycin (ADR) is active on solid tumors (osteosarcoma, breast and thyroid cancers) and lymphomas. With rubidazone (RBD) we obtain 2/3 of remissions in acute monoblastic leukemia, and it is easier to use than DNR and equally active on AML. RBD is also active on severe cases of lymphomas (lymphosarcomas and Hodgkin's disease). A new compound DEA 14 DNR seems interesting: experimental antitumor activity is high (compared to DNR, RBD and ADR) and it appears to possess activity on solid tumors in man.
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PMID:[Survey of anthracyclines derivatives in haematology (author's transl)]. 67 74

Between 1978 and 1988 (median follow up 5 1/2 years), 396 newly diagnosed adults with AML (age range 14-59 years, median 44) received STT comprising daily Adriamycin: 25mg/m2 for 3 days, Cytosine arabinoside (ara-C): 100mg/m2 bd and 6-thioguanine: 100mg/m2 bd, each for 7 days. A maximum of 6 cycles was administered with as short an intercycle time as possible. No further treatment was given. Complete remission (CR) was achieved in 243/396 patients (62%), 71 patients (18%) having resistant leukaemia and 82 (21%) dying within 6 weeks. Antecedent myelodysplasia and advanced age correlated unfavourably with achievement of CR (p = less than 0.001 and 0.005 respectively). Sixty nine patients continue in first remission between 2 1/2 and 12 years; the median duration of remission was 1 year. M3 morphology (p = 0.005) and absence of hepatosplenomegaly (p = 0.001) correlated favourably with duration of remission. Ninety one patients remain alive with an actuarial survival of 22% at 5 years. More recently, additional consolidation comprising high-dose ara-C and total body irradiation (TBI) with autologous bone marrow transplantation (ABMT) has been evaluated in an open study. CR has been achieved in 41/66 patients under the age of 50 but only 19/41 have proceeded to ara-C + TBI + ABMT. Twenty two have not (early recurrence 10, allogeneic BMT 4, debility 6, refusal 2). 11/19 who proceeded to ablative therapy continue in remission (4 treatment related deaths, 4 recurrences) as compared to 9/22 who did not. Currently the overall median duration of remission for the 41 patients intended to proceed is identical to that of age-matched historical controls illustrating the difficulties inherent in demonstrating benefit for the use of myeloablative therapy and ABMT in patients with AML in first remission.
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PMID:Short term therapy (STT) for acute myelogenous leukaemia (AML). 157 52

Since the differentiating effect of high-dose methylprednisolone (HDMP) on myeloid leukemic cells has been shown in one of our patients with acute myeloblastic leukemia (AML-M4), 27 previously untreated children with AML were given HDMP (20-30 mg/kg per day) combined with cytosine arabinoside (Ara-C; 3 mg/kg) for the first 2 weeks of induction therapy. Marked clinical improvement was observed in all patients with the exception of one who died within 24 hours of the treatment. Enlarged liver and spleen (greater than 5 cm) became nonpalpable in 3 (37%) out of 8 and 5 (100%) out of 5 patients, respectively, and bone marrow blasts decreased below 5% in 7 patients (27%) within 2 wk of HDMP and Ara-C treatment. Adriamycin (1 mg/kg) was added 2 wk after initiation of induction therapy. Twenty-two (84.6%) of the 26 patients achieved complete remission, 3 (11.5%) had partial remission and no response was obtained in one. Treatment was well tolerated. The addition of HDMP as a differentiating and/or cytolytic agent to conventional anti-leukemic chemotherapy increased the complete remission rate and prolonged the duration of remission of our AML patients.
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PMID:High remission rate in acute myeloblastic leukemia in children treated with high-dose methylprednisolone. 159 2

We describe a case of acute leukemia with t(4;11) (q21;q23) in a 3-month-old girl suffering from congenital hypothyroidism. The blast cells were cytochemically and immunologically classifiable as acute lymphoblastic leukemia of an early B-cell lineage (HLA-DR +, B4 +, CALLA-). but we treated this patient with a protocol designed mainly for acute nonlymphocytic leukemia, employing Adriamycin, vincristine, and cytosine arabinoside. Although the prognosis of this type of leukemia is known to be extremely poor, our patient is currently alive and in continuous complete remission lasting 35 months to date. This case may demonstrate a potential alternative therapeutic strategy for acute leukemia with t(4;11) as well as clinical evidence for the mixed-lineage characteristics of this condition. However, the pathogenetic role of congenital hypothyroidism in the development of acute leukemia is still uncertain.
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PMID:Successful treatment of acute leukemia with t(4;11) in an infant with congenital hypothyroidism. 224 Apr 80


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