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)

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

15 patients with acute myeloid leukaemia (AML) were treated with low-dose cytosine arabinoside (LD ARA-C). 2 patients had complete remissions, which lasted for 8 and 3 months, and 5 patients had a partial remission. 46% of the patients thus responded to LD ARA-C. This included 1 responding patient who had not previously responded to therapy with 6-mercaptopurine, thioguanine, or vinblastine. The 2 patients with complete remission did not show LD ARA-C-induced hypoplasia of bone marrow, although 1 had hypoplastic AML before therapy. Leukaemic cells from 1 patient showed in vivo maturation from M1 to M3 after LD ARA-C treatment. The present results, together with the published data, indicate that: a. LD ARA-C treatment, although it may have some toxic effects, is an effective treatment for some patients with AML, especially those with hypoplastic AML; b. Response to LD ARA-C can be obtained after one or several courses of treatment; c. LD ARA-C-induced remissions are sometimes obtained even in patients who fail in more conventional treatments; d. LD ARA-C-induced remissions can be achieved without bone marrow hypoplasia, and induction of hypoplasia by itself does not always result in complete remission; e. LD ARA-C can induce in vivo maturation of leukaemic cells. It is suggested that induction of remission in AML patients by LD ARA-C may result from either differentiation of leukaemic blast cells, cytotoxicity to leukaemic blasts, or both mechanisms acting together.
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PMID:Review of clinical and haematological response to low-dose cytosine arabinoside in acute myeloid leukaemia. 347 2

Five children treated for acute myeloid leukemia according to the BFM protocol AML 83 experienced first bone marrow relapse after 7, 10, 14, 18, and 30 months and were retreated for second remission induction. The chemotherapy consisted of mAMSA (100 mg/m2 per day i.v., days 1-3), ARA-C (100 mg/m2, twice daily, days 1-6), and VP 16 (150 mg/m2 per day, days 4-6). Four of the children achieved a complete second remission after one course of chemotherapy, and the fifth child died of pneumonia during bone marrow aplasia. All surviving children received an identical second course within 4-5 weeks, followed by maintenance chemotherapy. Remission duration was 0, 3, 4, 5, and 5 months. Toxicity was confined to heavy bone marrow depression with thrombocytopenia (nadir 2-7000, days 7-13) and leukocytopenia (nadir 0-400, days 8-14). Bleeding episodes could be prevented by substitution with platelets. Four patients experienced infections (pneumonia, septicemia). We conclude that combination chemotherapy using mAMSA, ARA-C, and VP 16 is effective in inducing a second remission in patients with early bone marrow relapse. The main side effect was considerable bone marrow toxicity.
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PMID:Effective remission induction in children with recurrent acute myeloid leukemia by mAMSA, Ara-C, and VP 16. 347 74

Two children with acute myeloid leukemia (FAB M1 and M2) experienced bone marrow relapse during maintenance chemotherapy 7 and 10 months after diagnosis. Low-dose ARA-C monotherapy (2 X 10 mg/m2 per day s.c. for 14 days) was then initiated, as suggested by others reporting induction of differentiation and achievement of remission without toxic side effects. In contrast to these reports, remission induction was not observed in the two children after low-dose ARA-C but was achieved by subsequent high-dose chemotherapy. However, blast cell characteristics revealed some alterations. Blast count and chromosome pattern remained unchanged. Cytochemistry revealed the appearance of esterase- (0----11%), 0----21%) and PAS- (0----74%, 0----45%) positive cells in the patients and a remarkable increase (patient 1: 0----71%) and decrease (patient 2: 90----12%) in acid phosphatase positivity. Expression of myeloid marker VIM D5 decreased distinctly (70----4%, 77----11%). However, the biologic relevance of these alterations remains in question. The failure to respond clinically to low-dose ARA-C in both children is discouraging.
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PMID:Alteration of blast phenotype after low-dose cytarabine in children with acute myeloid leukemia. 349 46

In the cooperative study AML-IGCI-84 27 children with AML (FAB M1 7X, M2 4X, M3 1X, M4 6X and M5 8X; 1 megakaryocytic leukemia) have been treated. The median initial white blood cell count was 18.0 G/l (range 1.8-1,350.0 G/l). 1 or 2 courses of induction therapy were used: I1 (aclacinomycin-A (ACLA-A), VP-16 and ARA-C) and I2 (daunorubicin (DNR), VP-16, and ARA-C). I2 was used only if bone marrow contained greater than 5% blast cells on day 21. I2 and consolidation treatment were identical with the current AML-BFM-83 protocol. 3 deaths before day 21 occurred (2 cerebral hemorrhages, 1 septicemia). 24 patients were evaluable for response, 20 (83.3%) achieved CR, 16 (66.7%) by I1, 4 after I2. 4 patients never reached CR, 3 of them had a PR after I1. M5 patients did badly (2 early deaths, 2 PR, 4 CR). All patients without CR after I1 received the whole AML-BFM-83 protocol. Comparison of the results of the 2 studies revealed a similar CR rate for I1 (our patients) and I2 (BFM data): 80.0% vs. 82.2% (calculated for patients who ever reached CR). CR was reached before consolidation in all our CR patients compared to 82.2% of BFM patients. Early CR may be of long term prognostic significance. Cardiotoxicity of induction may be reduced by substitution of DNR by ACLA-A.
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PMID:Aclacinomycin-A in the induction treatment of childhood AML. 352 63

In a phase I-II trial, 38 patients with acute myeloid leukemia (AML) were given single drug induction therapy with aclarubicin (ACM) according to two dosing schedules: treatment 1: 10 to 30 mg/m2/d to a maximum total dose of 300 mg/m2 or until development of unacceptable toxicity: treatment 2: 15 mg/m2/d in ten-day courses separated by ten-day intervals. Response rates were 15% with treatment 1 and 44% with treatment 2 (overall response rate 34%). Complete remission (CR) was achieved in 6 patients who had previously failed to respond to adriamycin (ADM). Toxicity was more frequent and more severe in those patients given more than 150 mg/m2 ACM per course. The main side effects were oropharyngeal mucositis and diarrhea. Three patients exhibited T wave inversion and one had an episode of auricular flutter. In a separate trial in 16 patients with AML we used cyclic chemotherapy combining ACM (20 mg/m2/d) and ARA-C (200 mg/m2/d) for seven consecutive days. Complete remission rate was 50%. Severe ventricular rhythm disorders were seen in two patients. In a phase I-II study, 19 patients with acute lymphoid leukemia (ALL) and 8 patients with non-Hodgkin lymphoma (NHL) were given ACM alone according to the regimen designated treatment 1 described above. Response rates were 11% (2/19) in ALL and 25% (2/8) in NHL. A review of the literature is presented in the discussion of the original trials reported herein.
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PMID:[Therapeutic trials of aclarubicin in previously treated acute leukemias and hematosarcomas]. 355 Jun 16

Five patients, 4 with ALL, 1 with AML received 8 cycles of HD-ARA-C (Capizzi protocol). One complete remission was achieved, 2 patients died shortly after cycle 1 and could not be evaluated. Two patients responded partially. Toxicity was considerable.
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PMID:[Therapeutic experiences with high-dose ARA-C and L-ASP]. 388 21

Four patients with acute leukemias resistant to various ARA-C containing regimens and one patient with rapidly progressive malignant nonseminomatous tumor of the testis, who failed to conventional therapy were treated with HD ARA-C from december 1979 to september 1980. The drug was monitored by HPLC in plasma and in CSF. The first patient received only one course of HD ARA-C, developed fever and died of septicemia ten days later. The leucocyte count of her AML (FAB 2) decreased from 120,000/microliter to 30,000/microliter on the third day after HD ARA-C. Patient 2 reached CR criteria of the bone marrow for 23 days, then resistant AML (FAB 2) recurred. A male patient of 30 years was treated for recurrent acute undifferentiated leukemia (AUL) with a high cumulative dose of 176 gs of ARA-C. The repeated courses of treatment included a period of 50 days of CR. Toxicity was remarkable including pulmonal and cerebral dysfunction. A fourth patient with monocytic leukemia did not respond to HD ARA-C, neither did the patient with the malignant teratoma. Adverse reactions were tolerable. Only the third patient suffered from severe toxicity, pneumonitis, blurring vision, cerebral dysfunction and dermatitis. His pretreatment regimen had included X-ray prophylaxis to the skull. Since there was no possibility to prolong the remission duration in 1980, we decided not to treat further patients with HD ARA-C. Nowadays bone marrow transplantation offers some patients a capability of eradication of the leukemic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Results of therapy with high-dose cytosine arabinoside]. 388 22

Nine patients with acute myelogenous leukaemia were treated with low-dose ARA-C (10 mg/m2, q 12h) for a planned 21 d. Complete remission was attained in only one patient (11.1%). Definite cytoreductive effect was seen in four additional patients. There was one treatment-related death. Haematologic toxicity occurred in all nine patients with sever thrombocytopenia most prominent. Severe hepatotoxicity precluded further ARA-C treatment in one patient. Because of toxicity only two patients were able to complete their scheduled 3 week courses of low-dose ARA-C. No evidence of ARA-C induced differentiation of leukaemic cells was noted on follow-up bone marrow examination during or shortly after the treatment course. The utility and indication for low-dose ARA-C therapy of AML remains to be determined.
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PMID:Low-dose ARA-C fails to enhance differentiation of leukaemic cells. 388 2

In two multicenter trials, a total of 576 patients with acute myeloid leukemia (AML) were treated and found to be evaluable. Two hundred forty-two patients were in a 1978 pilot study and 334 patients were in a 1982 randomized study. Ages were between 15 and 78 years (median, 48). The uniform remission induction therapy in both studies consisted of one to two courses of a 9-day combination of 6-thioguanine (TG) with cytosine arabinoside (ARA-C) and daunorubicin (DNR) [TAD9]. The timing and sequencing of TAD9 was designed according to cell kinetic effects of ARA-C. A complete remission (CR) was achieved in 65% (70% and 61%, respectively) of patients within a median of 33 days, and in 68% of responders after only one course. The CR rate in patients 60 to 78 years of age was 51% (66% and 39%, respectively). In the 1978 pilot study, different protocols of post-remission treatment were applied at the different centers: monthly 5-day maintenance, TAD9 consolidation, both consolidation and maintenance, or no further therapy. The group receiving treatment during CR showed 24% probability of remissions at 4 years v 0% probability of remissions in the untreated group. Between the different post-remission protocols, no significant differences were observed. Remission duration was not influenced by age, WBC, or morphologic cell type, but was longer in patients achieving CR within 30 days (P = .017). In the subsequent 1982 study, 145 patients in CR were randomized for TAD9 consolidation with or without monthly maintenance. The updated life-table analysis revealed a predicted rate of continuous remission at 2 1/2 years of 30% for the maintenance and 17% for the nonmaintenance arm (P = .003). These results of response and remission duration in adult patients of all ages support the validity of intensified induction therapy and of consequent myelosuppressive treatment in remission.
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PMID:Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group. 390 48


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