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)

In a multi-institutional study 26 patients with refractory acute myeloid leukemia were entered into a phase I/II study of HD-ara-C and mitox. HD-ara-C 3 g/m2 q 12h was given by 3h infusion on days 1-4. Mitox was started at 12 mg/m2/d on days 3, 4 and 5, and escalated to 4 and 5 doses of 10 mg/m2/d on days 2-5 and 2-6, respectively. From 24 patients presently evaluable for response, 12 achieved a CR and 2 a PR. 7 patients died of infectious complications within the first 4 weeks of treatment while persistent AML was found in 3 cases. Except for one death, possibly related to acute cardiomyopathy, toxicity was mild to moderate consisting of nausea and vomiting, mucositis and diarrhea. These data indicate a high anti-leukemic activity of HD-ara-C/mitox in AML refractory against conventional chemotherapy.
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PMID:High-dose cytosine-arabinoside and mitoxantrone in refractory acute myeloid leukemia: a clinical phase I/II-study. 352 60

The toxicity of high dose cytosine arabinoside (Ara-C) in 23 leukemic children aged 1.5 years to 16 years 11 months was evaluated. The group included 11 children with acute lymphoblastic leukemia (ALL), nine with acute nonlymphoblastic leukemia (ANLL), two with chronic myelocytic leukemia (CML) in blastic crisis, and one with Burkitt's lymphoma. Toxicity consisted of bone marrow suppression in all patients, with a mean nadir time of 11 days for platelets and granulocytes. All patients experienced nausea and vomiting; 12 of 23 had drug induced fever; seven of 23 conjunctivitis; five of 23 mucositis; four of 23 diarrhea, and one of 23 elevated transaminase with hyperbilirubinemia. Adverse reactions were mild and reversible in all patients. No serious neurologic toxicity was seen. The toxicity observed in four patients with prior cranial irradiation was not any different from nonirradiated patients. The only life-threatening effect was neutropenia, the consequences of which were generally well controlled with antibiotic therapy. While this agent was effective in induction of remission in AML patients resistant to standard doses of Ara-C, it had no significant effect in a very small number of patients with relapsed ALL and CML in blast crisis. Side effects of high dose Ara-C though relatively substantial are manageable enough to warrant wider scale efficacy trials of this agent in childhood leukemias and solid tumors.
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PMID:Toxicity of high dose Ara-C in children and adolescents. 359 53

Sixty-seven patients with newly diagnosed acute nonlymphocytic leukemia (ANLL) who were considered to be poor candidates for treatment with cytosine arabinoside (ara-C)/anthracycline antibiotic therapy were treated with high-dose ara-C (HDara-C) remission induction therapy. Thirty-four of the 67 patients had a hematologic disorder before developing acute leukemia or had a history of exposure to marrow toxins, 23 patients were greater than 70 years old, and 10 patients had medical problems that were felt to be a contraindication to therapy with an anthracycline antibiotic. Forty-two percent of patients entered complete remission (CR), whereas 22% failed to enter remission because of persistent leukemia. Treatment was associated with substantial toxicity varying from nausea and vomiting to irreversible cerebellar toxicity. Thirty-four percent of patients died during therapy. Poor performance status, a low serum albumin, and a low platelet count were associated with death during remission induction therapy, whereas a high pretherapy leukemic cell mass and a large number of residual leukemic cells in the marrow after six days of therapy were associated with treatment failure due to persistent leukemia.
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PMID:High-dose cytosine arabinoside as the initial treatment of poor-risk patients with acute nonlymphocytic leukemia: a Leukemia Intergroup Study. 380 62

Eleven cases of acute leukemia, 8 relapsed and 3 refractory to a conventional induction chemotherapy, were treated with a combination of intermediate-dose cytosine arabinoside (ara-C), adriamycin (ADM) and vincristine (VCR). They consisted of 9 ANLL and 2 ALL. The therapeutic regimen consisted of 1-hour infusion of ara-C of a dose of 500 mg/m2 every 12 hours for 6 days from days 3 to 8, ADM, 40 mg/m2, on day 1 and VCR, 1.4 mg/m2, on day 2. Among 11 cases in which an evaluation was possible, 7 obtained complete remission (CR). The CR rate was 77.8% in the 9 cases of ANLL. The toxicity of this regimen included the following: conjunctivitis in 4 of 11 cases (36%), nausea and vomiting in 9 of 11 cases (91%) and hair loss in all cases, although no toxicities of the central nervous system of liver were observed. The mean level of serum concentration of ara-C was above 10 microM at 15, 30 and 60 minutes after the initiation of infusion. The therapeutic effect of this regimen consisting of intermediate-dose ara-C is expected to be useful not only in induction of refractory and relapsed acute leukemia, but also in the postremission therapy of CR cases.
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PMID:[Therapeutic effects of a combination of intermediate-dose cytosine arabinoside, adriamycin and vincristine in relapsed acute leukemia]. 381 76

Fifty-two adults treated previously with either acute leukemia (43 patients) or blastic-phase chronic myelogenous leukemia (nine patients) received 4-demethoxydaunorubicin (20 to 45 mg/sq m) i.v. over 2 to 3 days. Three of the ten patients with acute lymphocytic leukemia achieved a complete remission (CR) lasting 5 to 7 weeks. Five of the 28 patients with acute nonlymphocytic leukemia achieved a CR lasting 5 to 80 weeks. All remissions were induced with one course of treatment with a median time to CR of 28 days (range, 22 to 40 days). None of the patients with blastic chronic myelogenous leukemia or secondary leukemia achieved a CR. The drug was well tolerated; mucositis (36%), nausea and vomiting (35%), and hepatic dysfunction (26%) were the most common side effects. Pharmacokinetic observations on five patients demonstrated multiphasic clearance of 4-demethoxydaunorubicin and extensive formation and prolonged retention of 4-demethoxy-13-hydroxydaunorubicin; that metabolite accumulated in plasma on repeated daily dosing. 4-Demethoxydaunorubicin has sufficient antileukemic activity in both acute lymphocytic leukemia and acute nonlymphocytic leukemia to warrant a prospective comparison, in combination regimens, against the conventional anthracyclines, daunorubicin and/or doxorubicin.
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PMID:Phase I and II clinical and pharmacological study of 4-demethoxydaunorubicin (idarubicin) in adult patients with acute leukemia. 385 96

Twenty courses of carminomycin were administered to 18 evaluable adult patients with acute leukemia (14 ANLL, 2 ALL, 2 CGL-BC). All but one received daily doses of 6-14 mg/m2 for 5 consecutive days. Two patients older than 60 yr had not prior chemotherapy and the others had refractory or relapsed disease. The median age was 60 yr. Three ANLL patients achieved complete remission for 8, 9 and 9 months respectively, with no maintenance therapy. None of these had proven clinical resistance to daunomycin and/or doxorubicin. Mucositis was dose-related and dose-limiting. Nausea and vomiting were rare. Alopecia was constant. Cardiac arrythmia was ascribed to carminomycin in two patients. One episode of cardiac failure seemed clearly drug-related and recovered with symptomatic treatment. In conclusion, encouraging antileukemic activity was observed with carminomycin in poor-risk patients. At doses up to 12 mg/m2 day X 5, extramedullary toxicity remained acceptable.
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PMID:Phase I-II evaluation of carminomycin in adults with acute leukemia. 385 51

Thirteen patients with refractory acute nonlymphocytic leukemia or with accelerated phase of chronic myeloid leukemia have been treated with high dose of cytosine arabinoside (Alcysten, Spofa). The drug was administered in doses of 3 g/m2/day. Six of 10 evaluable patients responded to the therapy. The mean duration of complete remission, achieved in 3 patients, was 18 weeks. The duration of partial remission ranged from 5 to 11 weeks. The treatment was well tolerated. Apart from expected hematological toxicity, transitory nausea and vomiting were the most frequently encountered side effects.
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PMID:Treatment of refractory leukemia with high-dose cytosine arabinoside. 385 54

A 44-year-old house-wife was admitted to the hematological clinic of our hospital on December 21, 1981 for the treatment of acute myeloid leukemia. Hematological examination showed severe anemia, leukocytosis and thrombocytopenia. She was soon started on DCMP therapy (Daunomycin, Cytosine arabinoside, 6-MP and prednisolone). After several repeats of remission and aggravation, she suffered from vertigo, nausea and vomiting in early August of 1982. The CT scan and angiography showed a mass lesion in the middle of the posterior cranial fossa. On August 26, surgical extirpation of the tumor locating in the vermis of the cerebellum was performed successfully. On gross examination the tumor revealed smooth yellowish-red surface, elastic in consistency and measured 40 X 40 X 30 mm in size. Histologically it comprised the leukemic cells. The pathology of the central nervous system due to leukemic cells was discussed in relation to the pertinent literature, including the CT findings and the indication of the surgical treatment.
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PMID:[Acute myeloid leukemia with intracranial tumor formation--case report]. 386 29

A Phase II study of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP), was conducted in 162 patients with various hematological malignancies in a multi-institutional cooperative study. THP was given intravenously at a dose of either 10-30 mg/body for 3-5 consecutive days or 40-60 mg/body at 3-week intervals. Of 22 patients with AML, complete remission (CR) was observed in 2 patients and partial remission (PR) in 2. Of 18 patients with ALL, CR was observed in 5 and PR in 3. Of 68 patients with NHL, CR was observed in 11 and PR in 22. Of 8 patients with HD, CR was observed in 4 and PR in 2. One CML case showed CR and one ATL case showed PR. PR was noted in one of 2 patients with mycosis fungoides. Overall remission rate was 43.1% (CR 23 cases and PR 33 cases). The predominant toxicity was myelosuppression. Leukopenia (less than 4,000/mm3) was noted in 67 (77.6%) and thrombocytopenia (less than 10 X 10(4)/mm3) in 24 (27.0%). Nausea/vomiting and anorexia were common, and were observed in 61 (43.3%) and 65 (46.1%) cases, respectively. Hair loss and cardiotoxicity were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for various hematological malignancies including acute leukemia and malignant lymphoma.
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PMID:[A phase II study of (2''R)-4'-0-tetrahydropyranyladriamycin (THP) in patients with hematological malignancies. THP Study Group]. 394 12

Twenty adult patients with relapsed acute nonlymphocytic leukemia were given intravenously the combination of pyrazofurin (PF) 7.5-30 mg/m2 x 1 on day 1 plus 5-azacytidine (AZA) 150-250 mg/m2/d in three divided doses for 5 days. Four patients are early deaths secondary to infection or hemorrhage and are invaluable for response. Three patients achieved a response (two patients had a CR, the third patient had a CR, relapsed, and then a PR). Duration of response was short (41-94 days). Hematologic toxicity was universal and similar at al dose ranges studied. The median pretreatment WBC and platelet counts were 500 and 32,000/microliter, respectively, and the nadirs were 500 and 15,000/microliter. Recovery only occurred in those patients who achieved a response. Nonhematologic toxicity consisted of skin rash (100% of the courses), mucositis (60%), myalgia (93%), nausea and vomiting (83%), and hypotension (47%). In conclusion, although there is interesting preclinical data to suggest that the combination of PF and AZA has synergistic cytotoxicity on leukemic cells, this human clinical trial demonstrates that the combination has significantly more nonhematologic toxicity than AZA alone and no therapeutic advantage over treatment with AZA alone.
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PMID:A clinical trial of pyrazofurin in combination with 5-azacytidine in acute adult nonlymphocytic leukemia. 616 6


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