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)

Twenty-two evaluable adult patients with relapsed, acute nonlymphocytic leukemia (ANLL) were treated with the combination of amsacrine (m-AMSA) and 5-azacytidine (AZA) as part of an Eastern Cooperative Oncology Group (ECOG) pilot study to evaluate efficacy and toxicity. Each drug was given in a dosage of 150 mg/m2 i.v. daily for 5 consecutive days. A complete response (CR) was obtained in 8 of 22 patients (36%) and a partial response was seen in two others, yielding an overall response rate of 45%. Median survival for all 22 patients was 2.5 months, but medium survival was 7.2 months (range 4.3-13 months) for those with a CR. Twelve of 22 died during the first 3 months, seven of these during the period of drug-induced aplasia. Moderate to severe toxicity included serious infection (16 of 22); nausea, vomiting, and diarrhea (19 of 22); and mucositis (10 of 22). There were four instances each of cardiac abnormalities and hepatic abnormalities but all reversed spontaneously. We conclude that this combination therapy cannot be recommended for further investigation in relapsed patients with ANLL since there was no notable increase in long-term survival and since there were 10 treatment-related deaths out of 22 patients.
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PMID:Amsacrine [4'-(9-acridinylamino)-methanesulfon-m-anisidide] (m-AMSA) and 5-azacytidine (AZA) for remission reinduction in patients with relapsed adult acute nonlymphocytic leukemia. An ECOG pilot study. Eastern Cooperative Oncology Group. 243 42

From December, 1985 to October, 1987, 16 patients aged from 14 to 62 (median 34) with acute leukemia in relapse (10 affected by ANLL and 6 by ALL) were treated with the following regimen: Idarubicin 12 mg/m2/day on days 1-2-3, Ara-C 600 mg/m2 twice a day from day 1 to 6. Twelve patients (75%) achieved complete remission (C.R.). Two (12%) died during the induction phase from alveolar pneumonitis. One patient was resistant. The median duration of C.R. and survival was respectively 12 (range 6 to 100 +) and 23 weeks (4 to 108 +). The median duration of granulocytopenia was 16 days (range 10 to 24 days). The most frequent non-hematological complications consisted of nausea, vomiting, diarrhea and mucositis. Four patients had hepatic and splenic microabscesses of suspected mycotic etiology, and one showed a transient cardiac arrhythmia. The C.R. rate obtained in this series may be considered satisfaying since all but 3 patients were on treatment at the time of relapse. Yet the short duration of C.R. suggests the opportunity of performing consolidation cycles or suprelethal therapy followed by bone marrow transplantation.
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PMID:Idarubicin combined with intermediate-dose cytosine arabinoside in the treatment of refractory acute leukemia. 249 85

A combination of aztreonam (AZT) and clindamycin (CLDM) was evaluated for severe infections associated with leukemia and related disorders. AZT is a monobactam antibiotic which has strong bactericidal effect against Gram-negative bacteria including Pseudomonas aeruginosa. CLDM which has strong antibacterial spectrum against Gram-positive and anaerobic bacteria, was chosen as a partner of AZT in order to complement the weak points of AZT. Fifty six patients were treated with the combination therapy. Among them, 51 patients were evaluable for the effectiveness. Five patients were excluded from the evaluation because 3 patients were subjected to additional therapy with other agents such as amikacin, miconazole and pulse therapy of a large dose of methylprednisolone, one had a fever episode apparently due to primary disease, and the remaining one was discontinued of the combination therapy of administration due to mild nausea after 3 days. Excellent responses were obtained in 17 (33.3%) patients and good responses in 20 (39.2%) patients, with a total rate of effectiveness of 72.5%. One patient with whom the combination therapy was stopped due to nausea, was included in the final evaluation of side effects. Side effects were observed in 2 patients of 50 and 40 years of ages (2/52, 3.8%), both of whom suffered with nausea. In the 50 years patient of acute myeloblastic leukemia, nausea occurred in a slight degree in 3 hours after the combined regimen was started. But, it disappeared during the continuation of the combination therapy. In the 40 years patient of acute myelomonocytic leukemia, mild nausea occurred after 3 day administration of the combined regimen. It disappeared soon after the cessation of the treatment. These results indicated that a combination of AZT and CLDM was an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.
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PMID:[Clinical evaluation of a combination therapy with aztreonam and clindamycin for severe infections in leukemia and related disorders]. 281 Jul 55

We conducted a Phase I-II trial of 4-demethoxydaunorubicin (idarubicin, IDR) in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) in 51 patients with relapsed or refractory acute nonlymphocytic leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis. Only 1 of 12 patients treated at the first dose level (idarubicin, 10 mg/m2/day for 3 days and ara-C, 25 mg/m2 i.v. bolus followed by 200 mg/m2 continuous infusion daily for 5 days) achieved aplasia and complete remission. The dose of idarubicin was subsequently increased to 10 mg/m2/day for 4 days with the ara-C dose held constant. Complete remission incidence for this dose schedule was: 7 of 31 patients with acute nonlymphocytic leukemia, 0 of 5 patients with acute lymphocytic leukemia, 0 of 1 patient with chronic myelogenous leukemia in blast crisis, and 1 of 2 patients with biphenotypic leukemia. Nonhematological toxicity included nausea, vomiting, mucositis, and abnormal liver function tests. Detailed pharmacological studies were performed to determine whether ara-C altered IDR metabolism or that of its main metabolite, 13-hydroxyidarubicinol or IDR clearance. A high degree of variability among patients was apparent and no consistent effect could be demonstrated. In summary, 9 of 37 patients (24%) with relapsed or refractory ANLL, including 1 patient with biphenotypic leukemia, achieved remission. We conclude that idarubicin in combination with ara-C is an active combination in patients with relapsed or refractory leukemia.
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PMID:4-demethoxydaunorubicin (idarubicin) in combination with 1-beta-D-arabinofuranosylcytosine in the treatment of relapsed or refractory acute leukemia. 291 Apr 65

Sixteen patients with previously treated acute nonlymphocytic leukemia or chronic myelogenous leukemia in blast crisis were given one to three courses of esorubicin by continuous infusion over 48 h. Dosage levels extended from 35 to 85 mg/m2. Four patients showed partial responses of short duration. Nonhematological toxicity observed at dosages of 55 to 85 mg/m2 were mucositis, diarrhea, skin rash, transaminitis, nausea, vomiting, and cardiac dysfunction. One patient receiving 85 mg/m2 developed acute florid congestive heart failure within hours of administration of the drug. Pharmacokinetic analysis revealed large interpatient variation in plasma drug levels. At the end of infusion, plasma decay of esorubicin was rapid initially but slow thereafter, with a terminal half-life of 20 to 54 h. The metabolite 4'-deoxy-13-hydroxydoxorubicin reached significant plasma levels. Total body clearance, renal clearance, volume of distribution at steady state, and mean residence time show little variation during dose escalation for both esorubicin and 4'-deoxy-13-hydroxydoxorubicin. Urinary excretion of esorubicin and 4'-deoxy-13-hydroxydoxorubicin accounted for 10.5 and 1.5%, respectively, of the administered dose.
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PMID:Pharmacokinetic and phase I evaluation of esorubicin (4'-deoxydoxorubicin) by continuous infusion over forty-eight hours in patients with leukemia. 316

Sixteen children with refractory hematological malignancies were treated with a combination of BH.AC, aclacinomycin-A, 6-MP and predonisolone (BH-AC.AMP protocol). They were ALL(6), ANLL(8), CML(1) and NHL(1). The CR ratio was 17% in ALL, 50% in ANLL, and blast crisis of CML was treated successfully but NHL failed in the induction remission. Major complications were vomiting, nausea, gastrointestinal bleeding, hematuria and hemorrhagic cystitis. More than 10 days or 120 mg/m2 administration of aclacinomycin-A was thought to induce more severe side effects.
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PMID:[BH-AC.AMP protocol in the treatment of refractory childhood acute leukemia]. 317 40

Both mitoxantrone and etoposide have been shown to be active in monotherapy trials of relapsed and refractory acute myelogenous leukemia (AML). This phase II study was undertaken to assess the antitumor activity and toxicity of the combination in refractory and poor-risk AML. The regimen consisted of mitoxantrone, 10 mg/m2/d intravenously (IV), and etoposide, 100 mg/m2/d as short infusion, both on days 1 to 5. Sixty-one patients are evaluable for response and toxicity. Twenty-one were primarily refractory to conventional courses of cytarabine, daunorubicin, and thioguanine; 20 patients had poor-risk first relapse (relapse within 6 months of first complete remission [CR] or relapse under continuous maintenance therapy); 11 had second or subsequent relapses; and nine developed secondary AML after myelodysplastic phase or myelofibrosis. Twenty-six patients (42.6%) attained a CR and seven (11.5%) a partial remission (PR). The median duration of continuous CR was 4.7 months, with a range of 21 days to 14 months, excluding four patients who underwent autologous bone marrow transplantation. Severe myelosuppression was observed in all patients, with a median time to CR of 49 days. Nonhematologic toxicity included stomatitis (mainly grade 1 and 2) in 41 patients, nausea (mainly grade 1 and 2) in 44, infections (mainly grade 3) in 33, and fever of unidentified origin in 11. Other than transient, mild cardiac failure in nine patients, in some of them combined with grade 1 to 2 tachyarrhythmia, no other drug-related cardiac events were observed. Two cases of early death within the first 6 weeks of treatment were registered. Thus, the combination of mitoxantrone and etoposide is a highly active and well-tolerated regimen for refractory and poor-risk AML.
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PMID:Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen. 342 60

A 57-year-old-male patient with acute myelogenous leukemia in second relapse who was refractory to BHAC . AMP [behenoyl arabinosyl cytosine (BHAC), aclacinomycin, 6-mercaptopurine and prednisolone (PSL)] and BHAC . DVP [BHAC, daunomycin, vincristine and PSL] was treated with an intermediate-dose cytosine arabinoside (ID Ara-C) regimen. This schedule consisted of a 1-h infusion of Ara-C at a dose of 500 mg/m2 every 12 h for 6 d (days 3-8), in combination with doxorubicin 50 mg/m2 on day 1 and vincristine 1 mg/m2 on day 2. The patient achieved a complete remission 23 days after completion of Ara-C and was treated with ID Ara-C (Ara-C days 3-6) as a consolidation. Remission duration was only 2.5 months. Plasma Ara-C concentrations were assayed by HPLC and the peak level was 6.7 micrograms/ml. Side effects were mild nausea, vomiting, alopecia and moderate skin rash.
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PMID:[A case of complete remission from acute myelogenous leukemia in second relapse achieved using an intermediate-dose cytosine arabinoside (ID Ara-C) regimen]. 345 5

Typhlitis is a neutropenic enterocolitis of varying severity. Its incidence is increasing, particularly in patients with acute myelogenous leukemia undergoing high dose cytosine arabinoside chemotherapy. The onset is heralded by prodromal fever, watery or bloody diarrhea, abdominal distension, and nausea during the phase of severe neutropenia. The symptoms may then localize to the right lower quadrant with an associated increase in systemic toxicity. The diagnosis can be confirmed in these and other less specific cases by serial reexamination and abdominal radiographs, ultrasonography, computerized tomograms, or radionucleotide scans. The mainstay of management is complete bowel rest with nasogastric suction and total parenteral nutrition. Broad-spectrum combination antibiotics are essential, as is the avoidance of laxatives or antidiarrheal agents. Granulocyte support may be helpful. Patients with a history of nonspecific gastrointestinal complaints or of true typhlitis, successfully managed nonoperatively, should have prophylactic bowel rest and total parenteral nutrition instituted at the beginning of further chemotherapy. Patients with ongoing severe systemic sepsis who do not respond to chemotherapy and those with overt perforation, obstruction, massive hemorrhage, or abscess formation require surgical intervention. All necrotic material must be resected, usually by a right hemicolectomy, ileostomy, and mucous fistula. Divided ileostomy for less severe cases may be useful. Failure to remove the necrotic focus in these severely immunocompromised patients is fatal. With adequate recognition of typhlitis and its precipitating factors, the incidence of complications can be reduced through prevention and timely surgical intervention. Although typhlitis developed in a quarter of our acute myeloblastic leukemia patients, use of this combined approach was successful in all cases.
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PMID:Typhlitis: selective surgical management. 345 80

Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.
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PMID:Aclarubicin in the treatment of elderly patients with acute nonlymphocytic leukemia. 346 85


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