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)

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

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

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

A 76-year-old woman with acute myelogenous leukemia with approximately 65% myeloblasts on bone marrow examination was treated daily with a combination of 4 megaU of leukocyte interferon IM and 1,000 mg cimetidine PO. During therapy there was a gradual decrease of bone marrow myeloblasts down to 9% and a normalization of peripheral white blood cells. The treatment was discontinued after 6 weeks because of increasing fatigue and anorexia. The general condition improved greatly during the following weeks and the patient entered complete remission, which has continued for 6 months so far. In the course of therapy there was a gradual appearance of antibodies showing a selective binding capacity to autochthonous leukemic cells with no tendency to increased binding to remission cells. The aim of this report is to stimulate a further evaluation of this form of therapy in additional AML patients whenever this might be justified as an alternative to conventional chemotherapy.
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PMID:Complete remission in a patient with acute myelogenous leukemia treated with leukocyte alpha-interferon and cimetidine. 658 32

Two metabolites of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) were found in the plasma and urine, and a hydrolytic product, arabinosylcytosine (ara-C) and its deaminated product, arabinosyluraci (ara-U), were found in a preclinical study using monkeys. Of a given dose, 96% was found as ara-U and 3% as ara-C in urine in 24 h. The plasma disappearance curve of BH-AC is biphasic; the half-life of the initial phase is 40 min and that of the second phase is 120 min. At 8 h the BH-AC level is 21.9 micrograms/ml and falls exponentially to 3.6 micrograms/ml by 12 h. Ara-C was detected at the levels of 0.4-0.6 microgram/ml for 4 h. Comparative data of pharmacokinetic parameters among BH-AC, ara-C, and O2,2'-cyclocytidine showed that BH-AC had the longest plasma half-life, the smallest elimination-rate constant and the smallest excretion-rate constant. The plasma-clearance study of BH-AC in 13 patients showed essentially a pattern similar to that in monkeys; the plasma t 1/2 of 60 min in the first phase and of 180 min in the second. The BH-AC level at 2 h is 15.4 micrograms/ml, and 1.8 microgram/ml at 8 h. Initial phase I study of BH-AC was evaluated in 14 patients with leukemia and other malignancies. The starting dose was 1.5 mg/kg given as a single IV infusion for 3. The doses were when escalated up to 5.0 mg/kg. No side effects were noted with a single dose schedule. Daily consecutive infusions of 2.0 mg/kg-6.0 mg/kg for 4-21 days resulted in two patients having nausea, two anorexia, and one developing skin eruptions. Significant hematologic effects were noted with the daily infusion. One patient with acute myeloblastic leukemia achieved complete remission with 5.0 mg/kg BH-AC given daily for 21 days. It pharmacologic features, minimal toxicity, and the capability of inducing complete remission in acute leukemia indicate that BH-AC undoubtedly deserves further prospective clinical trials.
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PMID:Pharmacologic and clinical studies of N4-behenoyl-1-beta-D-arabinofuranosylcytosine. 676 63

The results of an autopsy of an 80-year-old Japanese male with acute myeloid leukemia who died of spontaneous rupture of the spleen are reported. The patient was admitted because of anorexia, fatigue, weight loss, and multiple skin eruptions. Hematological examinations indicated a rapid increase in myeloblasts. The patient collapsed on the 28th hospital day, immediately after complaining of severe epigastralgia and vomiting. He died ten hours later. The autopsy revealed extensive leukemic infiltration of the bone marrows, spleen, lymph nodes, skin, and other internal organs. The spleen was enlarged and was ruptured in places at the hilar portion. Massive intraperitoneal hemorrhage from the rupture was the direct cause of death. The mechanisms of splenic rupture are discussed.
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PMID:Spontaneous rupture of the spleen in acute myeloid leukemia. 694 31

Relapses in nine patients with acute myelocytic leukemia were treated with a combination of aclarubicin (ACR) and cytosine arabinoside (ara-C). ACR, 40 mg/m2/day, was administered daily by intravenous injection from day 1 to day 3 and ara-C, 60-80 mg/m2/day, divided into 2 doses, was given every 12 h by intravenous infusion from day 1 to day 7. Depending on the state of the bone marrow, ACR-ara-C regimen was modified in administration period and repeated after the resting periods of at least 7 days. Complete remission was obtained in 7 of 9 patients (77.8%). The time required for achieving the complete remission varied from 20 to 55 days with a median of 39 days. The duration of complete remission was from 8 to 52 weeks with a median of 22 weeks. Side effects on digestive system such as nausea, vomiting and anorexia, were seen in all patients, although they were managed by symptomatic treatment. The results indicate the effectiveness of this ACR-ara-C regimen in the clinical management of acute nonlymphocytic leukemia.
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PMID:Treatment of relapsed acute myelocytic leukemia with a combination of aclarubicin and cytosine arabinoside. 695 Jun 58

Indicine N-oxide, the first pyrrolizidine alkaloid N-oxide to be studied in the treatment of cancer in humans, was administered to ten patients: four children and two adolescents with refractory acute lymphocytic leukemia and four adults with refractory acute nonlymphocytic leukemia (three acute myelocytic, one myelomonocytic). Two patients, a 4-year-old boy with acute lymphocytic leukemia and a 22-year-old man with acute myelocytic leukemia, achieved complete remission lasting 3 and 5+ months, respectively. Another 15-year-old male with acute lymphocytic leukemia had a partial remission for four months. Toxicities included bone marrow suppression, mild anorexia and nausea, and transient elevation of liver enzymes. Jaundice and liver failure, presumably induced by drug, occurred in two patients.
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PMID:Activity of indicine N-oxide in refractory acute leukemia. 701 59

A nationwide multi-center cooperative phase II clinical study of irinotecan hydrochloride (CPT-11) was conducted to evaluate its efficacy in intractable malignant lymphoma and acute leukemia. In malignant lymphoma, one course of CPT-11 consisted of intravenous drip infusion at a dose of 40 mg/m2 once daily for 3 consecutive days, performed once a week. In acute leukemia, one course of CPT-11 consisted of intravenous drip infusion at a dose of 15 to 20 mg/m2 a day twice daily for 7 consecutive days (1 cycle), performed every 2 to 4 weeks. Among the 79 patients with malignant lymphoma and 50 patients with acute leukemia enrolled in the study, 66 and 41 patients, respectively, completed treatment. These patients had all undergone chemotherapy prior to treatment. Among the malignant lymphomas, the response rate in non-Hodgkin's lymphoma (NHL), including 9 CRs, was 42% (26/62, 95% CI: 30-54%); of these there was a response rate of 39% (5/13), including 1 CR, in adult T-cell leukemia (ATL) as well. In Hodgkin's disease (HD), on the other hand, there were no cases in which efficacy was demonstrated (0/4). The overall response rate in malignant lymphoma was 39% (26/66), and the response rate even among the recurrent intransigent cases was 42% (16/38). The 50% survival time (MST) in the 74 eligible cases of malignant lymphoma was 153 days. In acute leukemia, on the other hand, partial remission was observed in 2 of 17 cases (12%) of acute lymphocytic leukemia (ALL), but no cases of remission were observed in the 24 patients with acute myelogenous leukemia (AML). The overall remission rate in acute leukemia was 5% (2/41, 95% CI: 1-14%). The principal adverse effects were myelosuppression in malignant lymphoma and gastrointestinal symptoms, including diarrhea, nausea/vomiting, anorexia and abdominal pain, in both malignant lymphoma and acute leukemia, and there was little organ damage to the heart, liver or kidney. Myelosuppression and gastrointestinal adverse effects were severe in some of the patients, so caution is required. Based on the above findings, CPT-11 appears to be efficacious in the treatment of non-Hodgkin's lymphoma.
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PMID:[Late phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies]. 821 Feb 56

An early phase II study of CPT-11 (irinotecan hydrochloride) was conducted in patients with hematological malignancies by 4 administration regimens in a cooperative study involving 13 institutes in Japan. The overall response rate was 23% (7/30) for non-Hodgkin's lymphoma, 33% (1/3) for Hodgkin's disease, 18% (2/11) for acute lymphoblastic leukemia and 7% (1/15) for acute myelogenous leukemia. One PR was also obtained in a patient with chronic myelogenous leukemia. Among responders, 6 relapsed and refractory malignant lymphomas (ML) and 2 relapsed and refractory acute leukemias (AL) were involved. The response rates in ML with the regimens B (40 mg/m2 for 5 days every 3-4 weeks) and C (40 mg/m2 for 3 days every weeks) were 31% (5/16) and 33% (3/9), respectively. The other regimens (regimen A, 200 mg/m2 once a day every 3-4 weeks and regimen D) resulted in no response. Responses in AL were only observed in regimen D (20 mg/m2 twice a day for 7 days every 3-4 weeks). Major toxicities were leukopenia (91%), nausea/vomiting (74%), diarrhea (73%) and anorexia (64%). The incidence of severe gastrointestinal symptoms was higher in regimen B than regimen C. Further studies are warranted to confirm the effectiveness and safety of CPT-11 against ML and AL. The recommended administration schedule was regimen C for ML and regimen D for AL.
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PMID:[An early phase II study of CPT-11 (irinotecan hydrochloride) in patients with hematological malignancies]. 829 18


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