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)

Thirty-one children with ANLL were treated using the 12th-ANLL Protocol of the Tokyo Children's Cancer Study Group incorporating an ACMP 2-step regimen. Induction therapy consisted of two 4-day courses of adriamycin (ADR) and cytosine arabinoside (ARA-C) given with a 7-day interval. Those patients who achieved remission were given one more course as early intensification. Late intensification consisted of a 5-day course of ARA-C and one dose of ADR which was repeated until the cumulative dosage of ADR reached 465 mg/m2. After this point, treatment was divided into 2 courses. Both courses included ARA-C and one course had achlacinomycin in addition. Twenty-seven children (87%) attained remission after one or two courses of induction therapy. Kaplan-Meyer analysis revealed that the continuous complete remission rate and event-free survival were 71% and 51%, respectively, 5 years after diagnosis. Toxicity was minimum with only one death during the remission. These results are encouraging and warrant further trials.
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PMID:Improved prognosis of acute nonlymphocytic leukemia in children: results of the 12th-ANLL protocol of Tokyo Children's Cancer Study Group. 179 13

From 1982 to 1990, 340 children with newly diagnosed ANLL entered two consecutive AIEOP trials: LAM 8204 (1982-1987) and LAM 87 (1987-1990). Patients in both studies received identical remission induction with Daunorubicin and ARA-C. In the first study (LAM 8204) 167/171 patients were consolidated with four courses of DAT, followed by six additional courses of continuation therapy with three drug pairs given sequentially. Periodic intra-thecal ARA-C was used for CNS prophylaxis. For patients remaining on protocol, the OFS and EFS probability at 8 years was 35% and 30%, respectively. Induction response and EFS were adversely predicted by FAB MS subtype and hyperleukocytosis. In LAM 8204 trial there were 30 withdrawals represented by patients undergoing allogeneic (14) or autologous (16) BMT. For these patients the DFS probability at 5 years was 64% and 50%, respectively. On LAM-87 trial, 136/169 patients were evaluable and 98 (76%) attained CR. After consolidation with one course of DAT, patients with an HLA-identical donor underwent allogeneic BMT and those lacking a matched donor were randomized to receive either autologous BMT or the LAM 8204 postremission chemotherapy. The 2-year probability of DFS for allografted patients was 76% significantly higher (P = 0.0001) than that observed for patients on chemotherapy (12%) or autologous BMT (31%) arms.
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PMID:Allogeneic vs autologous BMT vs intensive chemotherapy in childhood AnLL during first complete remission: AIEOP experience. AIEOP Cooperative Group. 185 93

Ninety-two elderly patients (ages 50-70) with "de novo" acute myeloid leukemia were given induction chemotherapy consisting of aclacinomycin-A (ACLA) (100 mg/m2/day x 3) and cytosine arabinoside (ARA-C) (100 mg/m2 day, continuous infusion, 7 days). Fifty-one patients (55%) achieved complete remission (CR), 8 patients exhibited drug resistance and 33 patients died during chemotherapy or aplasia. Three patients had severe cardiac toxicity. The only prognostic factor significantly affecting CR was the initial leukocyte count. After consolidation using ACLA (80 mg/m2/day x 2) and ARA-C (100 mg/m2/day x 5), 47 CR patients were randomly assigned to 2 different treatment arms: 23 patients (Group A) received intensive sequential chemotherapy consisting of 4 monthly courses of 8 different drugs while 24 other patients (Group B) were given ACLA and ARA-C at regular intervals, associated with continuous chemotherapy consisting of 6-mercaptopurine, methotrexate and androgens. The probability of disease-free survival at 2 years was significantly higher (33 +/- 22%) for Group B patients than for Group A (13 +/- 16%) (P less than 0.05). We conclude that continuous maintenance chemotherapy may be useful in increasing the number of long-term survivors, at least in the elderly who have not received very intense consolidation chemotherapy following CR.
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PMID:Treatment of acute myeloid leukemia in elderly patients: the influence of maintenance therapy (BGM 84 protocol). 219 31

In patients with acute myeloblastic leukemia incomplete response to induction chemotherapy and short disease-free survival may be related to cell kinetic quiescence of leukemic cells. In this in vitro study, we tested the hypothesis that treatment with cytokines and subsequent chemotherapy (ARA-C, daunorubicin) can increase proliferation and enhance leukemic cell kill. We evaluated the effects of recombinant human interleukin-3 (rh-IL-3), granulocyte-macrophage colony stimulating factor (rhGM-CSF) and granulocyte colony stimulating factor (rhG-CSF) alone and in combination on AML (N = 11) and blastic phase CML (N = 3) samples. Cellular DNA and RNA, incorporation of bromodeoxyuridine (BrdU), cell growth fraction, cell viability, and differentiation markers were evaluated in vitro. A decrease of the quiescent cell population (p = 0.003) and an increase in S-phase cells (p = 0.001) was observed in 8/11 AML samples treated with cytokine combinations. Pronounced heterogeneity or proliferative response was seen between individual cases and different cytokines, but in the majority of the samples IL-3 was most effective. Significantly increased Ki67 expression (p = 0.009) and BrdU incorporation (p = 0.01) were also found after exposure to cytokines indicating an increase in growth fraction. DNA synthesis time was unaffected. Eight samples of AML were treated for 24 hr with ara-C following 2 days of in vitro cytokine incubation. Evaluation of leukemic cell kill showed increased cytotoxicity in three of those five samples which had significant depletions of G0 cells and increases in S-phase. None of the leukemic samples without recruitment from G0 had an increase in ARA-C cytotoxicity. This study provides detailed cell kinetic analysis of cytokine effects on AML blasts and provides a rationale for a novel approach to the treatment of AML.
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PMID:Kinetic rationale for cytokine-induced recruitment of myeloblastic leukemia followed by cycle-specific chemotherapy in vitro. 224 6

In order to reduce the incidence of severe complications noted with regimens containing high-dose cytarabine (HD ARA-C), wer used a combination of mitoxantrone (MTZ) in optimal dosage (12 mg/m2/day for 5 days) and cytarabine in intermediate dosage (1 g/m2 twice daily for 3 or 5 days). Thirty patients aged 2 to 65 years (median 51) with acute myeloid leukemia (AML), either refractory (8 patients), in first relapse (20 patients) or chemoinduced (2 patients), received this program. Seventeen (57%) achieved complete remission (CR). The main prognostic factor was the previous use of HD ARA-C (21% CR for patients previously treated with HD ARA-C versus 87% for patients treated with conventional doses: P less than 0.001). Mucositis was the most significant extrahematologic side-effect. There was no severe cerebellar toxicity. Two patients had transient congestive cardiac failure. This regimen is effective and relatively well tolerated in heavily pretreated patients. It can be used either as induction or consolidation therapy in AML.
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PMID:Mitoxantrone and intermediate-dose cytarabine in relapsed or refractory acute myeloblastic leukemia. 229 Jul 8

We conducted a randomized multicenter trial comparing low-dose cytarabine (LD ARA-C) (20 mg/m2 for 21 days) with an intensive chemotherapy (rubidazone [a daunorubicin-derived agent], 100 mg/m2 for 4 days, ARA-C 200 mg/m2 for 7 days) in 87 patients over 65 years of age with de novo acute nonlymphocytic leukemia (ANLL). Forty-one patients received LD ARA-C and 46 received intensive chemotherapy. The number of complete remissions (CRs) but also of early deaths was higher in the intensive chemotherapy group, while partial remissions (PRs) and failures were more frequent in the LD ARA-C group (P less than .001). Infectious complications during induction treatment were more numerous and more severe in the intensive chemotherapy group (P less than .01). Patients treated with LD ARA-C required fewer RBC transfusions (P less than .02), fewer platelet transfusions (P less than .01), and had a shorter hospital stay for induction treatment (P less than .01). Overall survival and CR duration were not significantly different in either group. In the LD ARA-C group, the survival of patients with PR and those of patients in CRs was identical. We conclude that in a selected group of elderly patients with de novo ANLL a higher number of CRs may be obtained with intensive chemotherapy, but that with LD ARA-C, the number of early deaths is lower, and long-lasting PRs are obtained, resulting in a similar overall survival.
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PMID:Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. 229 70

From ten consecutive patients with acute myeloid leukemia leukemic cells were isolated and cultured with and without 10(-6), 10(-7) and 10(-8) M 1.25(OH)2D3 (vit D3), retinoic acid (RA) cytosine-arabinoside (ARA-C) and 1.0, 1.25 and 1.5% dimethyl sulfoxide (DMSO). Maturation was measured with a comprehensive panel of qualitative and quantitative parameters of maturation. Six of those ten leukemias showed significant (p less than 0.01) changes in at least three parameters after exposure to either one of the differentiation inducers. Vit D3 induced maturation in four leukemias, in three of them clearly in monocytic direction. ARA-C showed changes in one leukemia in only three parameters not pointing to either granulocytic or monocytic direction. Maturation in granulocytic direction was observed after exposure to RA in one leukemia. Maturation induction was observed in six out of ten freshly isolated leukemic cells with vit D3 being the most potent inducer of maturation in monocytic direction. The data about inducibility of maturation in freshly isolated human leukemic cells are reviewed and discussed.
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PMID:Maturation induction in freshly isolated human myeloid leukemic cells, 1.25 (OH)2 vitamin D3 being the most potent inducer. 254 44

High-dose cytarabine (HDARA-C) is an effective but toxic treatment for acute myeloid leukemia (AML). In order to reduce the incidence of severe complications noted with HDARA-C-containing regimens, we used a combination of intravenous (IV) idarubicin (IDARUB) at optimal dosage and cytarabine (ARA-C) at intermediate dosage. Thirty-five patients aged 23 to 78 years (median, 56) with AML in first relapse received IDARUB, 8 mg/m2/d for five days, and ARA-C, 1 g/m2 every 12 hours for six doses. Of the 35 patients, 21 achieved a complete remission (CR), four had a partial remission (PR), four died in aplasia, and six were nonresponders. The only factor influencing the CR rate was the duration of the first CR (35% for patients relapsing before 16 months v 83% for patients relapsing after 16 months, P = .003). Mucositis was the most significant extrahematologic side effect. Diarrhea, skin toxicity, and hepatic disturbances were rare and mild. There was no cerebellar toxicity, even in 25 patients greater than 50 years of age. This regimen is effective and well tolerated even in elderly patients, and could be used either as induction or consolidation therapy for the treatment of AML.
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PMID:Treatment of relapsed acute myeloid leukemia with idarubicin and intermediate-dose cytarabine. 264 39

21 patients with hematological neoplasias (8 ALL, 4 AML, 4 NHL, 5 HD) were treated with high dose therapy and autologous bone marrow rescue (ABMT). At the time of ABMT 12 patients were in CR, 6 in PR and 3 in relapse. 66% of the patients were at high risk at the time of diagnosis. Before ABMT patients received an ablative regimen such as cyclophosphamide or ARA-C, VP-16, DNR and 12 Gy TBI in 6 fractions. In 9 patients the bone marrow was treated in vitro with monoclonal antibodies and complement. The hospital stay was a median 33 (24-57) days and isolation 19 (9-49) days. Complications were septicemia (7), herpes stomatitis (7), infections (6), fungal sepsis (1) and hemorrhagic cystitis (2). Late complications (up to 6 months after ABMT) were pneumococcal sepsis (1), cerebral toxoplasmosis (1) and herpes zoster (3). 10 of 19 evaluable patients are alive and relapse-free 1-33 months (median 10) after ABTM, and 3 of 10 more than 2 years later: 4 of 5 were transplanted in 1. CR, 4 of 6 in greater than or equal to 2. CR and 2 of 8 in PR. 4 patients are living in therapy sensitive relapse 2, 11, 11 and 39 months after ABMT in 2. CR or PR. 5 patients died 1-13 (median 3.5) months on relapse, 2 of 21 from septicemia. The morbidity of ABMT is comparable with conventional high dose chemotherapy. Relapse-free survival was significantly influenced by the remission status at ABMT. Long-term survivors can be expected even in patients with high risk hematological malignancies. However, only wider trials will serve to establish the efficacy of ABMT.
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PMID:[Autologous bone marrow transfusion in the treatment of adults with hematologic neoplasms. Experiences from Bern]. 266 30

Seventeen elderly patients with acute nonlymphocytic leukemia (EP-ANLL) were treated with cytarabine, either 1.5 g/m2 or 2.0 g/m2 q 12 h for 4 days [attenuated high-dose ARA-C (HDARAC)]. One complete and one partial response was seen in 15 evaluable cases. Toxicity, evaluated in all 17 patients, was severe, with 47% showing a variety of Eastern Cooperative Oncology Group grade 3, 4, or 5 toxicities. Forty-one percent of all patients died within 33 days of initiating treatment. We conclude that attenuated HDARAC is ineffective in inducing remission and is very toxic in the EP-ANLL.
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PMID:Attenuated high-dose cytosine arabinoside in the treatment of the elderly patient with acute nonlymphocytic leukemia. An Eastern Cooperative Oncology Group Pilot Study. 272 77


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