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)

Samples from 15 patients with acute myeloid leukemia (AML) were studied in a colony-inhibition assay of drug sensitivity. In vitro sensitivity to both Adriamycin (Adr) (1-h incubation) and cytosine arabinoside (AraC) (24-h and continuous incubation) were determined, as were the tritiated thymidine suicide indices (SI) during the 24-h incubation with AraC. The sensitivity of the proportion of cells entering S-phase during the 24-h incubation was also evaluated. Using discriminant analysis a function was derived to separate the patients into two groups, those who failed remission induction therapy, or nonresponders (group 1), and those who entered complete remission (group 2). The only variables that contributed to prediction were the Adr (1 h) and Ara-C (24 h) results. Overall, 87% (13/15) of the patients were correctly grouped using this function, with a confidence level for nine of these 13 patients of greater than 80%. Adr and AraC results contributed equally to the prediction.
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PMID:Adriamycin and cytosine arabinoside contribute equally to prediction of response in acute myelocytic leukemia with improved confidence level. 385 5

Based on the in vitro experiments which showed the capacity of Aracytine (AraC) to induce differentiation of leukemic cells, low dose AraC treatment of patients with acute myeloid leukaemia (AML) or myelodysplastic syndromes (MDS) has been available since 1980. Many studies involving only small numbers of patients have demonstrated contradictory results regarding the efficacy or the mechanism of action of this regimen. A retrospective clinical study is presented, including 159 patients treated in 11 French institutions and 1 German institution (AML: 99 patients; MDS: 38 patients). The study confirms the efficacy of low dose AraC, especially in elderly patients with hypoplastic AML. Although, less severe than with high dose chemotherapy, toxicity needs regular monitoring. The mechanism of action cannot be ascertained by this clinical study, however half of the complete remissions were obtained with no bone marrow aplasia. Studies with low dose AraC and/or other in vitro differentiating agents need to be continued.
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PMID:[Treatment of malignant hemopathies with aracytine in low doses. Analysis of 159 cases]. 386 52

10 adult patients (age 27-62 years) with refractory or relapsed acute nonlymphocytic leukemia were treated with high dose cytosine arabinoside (HDAraC: 3 g/m2 q 12 h by IV infusion, d 1-6) either alone (7 patients) or with additional treatment, consisting of bone marrow transplantation (1 patient), m-AMSA (1pt.) and VP16 (1 patient). All patients had received conventional dose AraC (CDAraC); 8 patients were resistant to CDAraC, having failed 1 or more courses of CDAraC just before treatment with HDAraC. Recovery of granulocyte count (0,5 X 10(9)L) occurred at a median of 26 d (23-27 d) after initial therapy, and recovery of platelet counts (50 X 10(9)/L) at a median of 24 d (22-27 d). 6 patients became severely septic, 3 of them requiring granulocyte transfusions. Consequently, sophisticated blood banking facilities and supportive care are required. The non-myeloid toxicities associated with HDAraC were not severe. Vomiting (9/10), erythematous skin rash (4/10), conjunctivitis and photophobia (2/10) were found most commonly. CNS-toxicity, pulmonary toxicity or drug fever were not observed. 4 patients achieved a complete remission and 1 a partial remission. 2 patients failed to respond and 3 patients died during the period of pancytopenia. Thus, HDAraC is effective treatment for refractory or relapsed ANLL, even in cases of apparent resistance to CDAraC.
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PMID:[High-dose cytosine arabinoside in the treatment of recurrent or acute refractory myeloid leukemias]. 388 19

28 consecutive patients (age 15-58 years) with refractory acute leukaemia (24 AML, 4 ALL) have been treated with high or intermediate dose cytosine arabinoside (AraC). Twenty patients received AraC at a dose of 3000 mg/m2, twice daily for 6 days (13 patients AraC alone, 7 patients AraC and doxorubicin) and 8 patients received AraC at a dose of 1000 mg/m2, twice daily for 6 days and daunorubicin. 10 of the 20 patients treated with high dose AraC achieved a complete remission (50%) and 2 a partial remission. No patients in the intermediate dose AraC group achieved a remission (p = 0.05). Toxicity of these protocols was acceptable. Vomiting, headache, somnolence, fever, conjunctivitis, and minor cardiac arrhythmias were found most frequently. The pancytopenic period ranged from 16-30 days for the high dose protocol and 14-23 days for the intermediate dose protocol. Sophisticated isolation and blood banking facilities are required in this period. Median duration of remission was 6 months. Results obtained are in favour of the high dose protocol in refractory leukaemia. Only a large dosage increment of AraC can overcome refractoriness of leukaemic blast cells.
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PMID:Experience with intermediate and high dose cytosine arabinoside in refractory acute leukaemia. 635 50

Although cytosine arabinoside (araC) can induce a remission in a majority of patients presenting with acute myeloblastic leukemia (AML), a minority fail to respond and moreover the drug has less effect in acute lymphoblastic leukemia (ALL). The carrier-mediated influx of araC into purified blasts from patients with AML, ALL, and acute undifferentiated leukemia (AUL) has been compared to that of normal lymphocytes and polymorphs. Blasts showed a larger mediated influx of araC than mature cells, since mean influxes for myeloblasts and lymphoblasts were 6- and 2.3-fold greater than polymorphs and lymphocytes, respectively. Also, the mean influx for myeloblasts was fourfold greater than the mean for lymphoblasts. The number of nucleoside transport sites was estimated for each cell type by measuring the equilibrium binding of [(3)H]nitrobenzylthioinosine (NBMPR), which inhibits nucleoside fluxes by binding with high affinity to specific sites on the transport mechanism. The mean binding site numbers for myeloblasts and lymphoblasts were 5- and 2.8-fold greater, respectively, than for the mature cells of the same maturation series. The mean number of NBMPR binding sites for myeloblasts was fourfold greater than for lymphoblasts. Patients with AUL were heterogeneous since blasts from some gave values within the myeloblastic range and others within the lymphoblastic range. The araC influx correlated closely with the number of NBMPR binding sites measured in the same cells on the same day. Transport parameters were measured on blasts from 15 patients with AML or AUL who were then treated with standard induction therapy containing araC. Eight patients entered complete remission, while seven failed therapy, among whom were the three patients with the lowest araC influx (<0.4 pmol/10(7) cells per min) and NBMPR binding (<3,000 sites/cell) for the treated group. In summary, myeloblasts have both higher araC transport rates and more nucleoside transport sites than lymphoblasts and this factor may contribute to the greater sensitivity of AML to this drug. AraC transport varied >10-fold between leukemic blasts and normal leukocytes, but transport capacity related directly to the number of nucleoside transport sites on the cell. Finally, low araC transport rates or few NBMPR binding sites on blasts were observed in a subset of patients with acute leukemia who failed to achieve remission with drug combinations containing araC.
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PMID:Cytosine arabinoside influx and nucleoside transport sites in acute leukemia. 694 29

17 patients (age 15-58 years) with refractory acute leukaemia (14 AML, 3 ALL) were treated with high dose cytosine arabinoside (AraC) at a dose of 3000 mg/m2, twice daily for 6 d (13 patients with AraC alone, 4 patients with AraC and doxorubicin). 9 patients achieved complete remission (53%) and 2 a partial remission. Although sophisticated isolation and blood banking facilities are required during the pancytopenic period, the toxicity of this treatment was acceptable. Vomiting, headache, somnolence, fever, conjunctivitis and cardiac arrhythmias were found most frequently. The unexpected pulmonary failure in 3 patients was worrisome. The duration of remissions was from 1 to 12 months. Results obtained with high dose AraC are satisfactory and hold promise for the treatment of patients with previously untreated AML.
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PMID:High dose cytosine arabinoside in the management of refractory acute leukaemia. 695 4

The application of hematopoietic growth factors in the treatment on acute myeloid leukemia (AML) may principally aim at shortening the period of treatment associated neutropenia and reducing the rate of infectious complications by their post-therapeutic administration but may also be used to increase the sensitivity of leukemic blasts to antileukemic therapy by pretherapeutic growth stimulation. Both aspects were addressed in subsequent clinical phase II studies and preclinical investigations. In a first clinical trial, 36 patients with high-risk AML received granulocyte-macrophage colony-stimulating factor (GM-CSF) after successful cytoreductive chemotherapy and experienced a shortening of the period of post-therapeutic neutropenia by 6 to 9 days, leading to a significant reduction of treatment-associated deaths from 39% to 14%. In preclinical studies an enhancement of the cytotoxicity of cytosine arabinoside (AraC) on leukemic blasts could be shown by pretreatment with GM-CSF or IL-3. Investigations on the impact of hematopoietic growth factors on the intracellular metabolism of AraC indicated that this effect was primarily mediated by an increase in the activity of DNA-polymerase-alpha. The evaluation of different doses of AraC showed the most marked increase after the combination of GM-CSF with conventional rather than high doses of AraC. Based on these preclinical experiments, a prospective randomized trial was subsequently initiated investigating the effect of GM-CSF before and during induction, consolidation, and the first two cycles of maintenance chemotherapy in newly diagnosed AML. This ongoing trial has enrolled 67 patients at the current time. An early interim analysis showed no differences in remission rates but a tendency toward a longer remission duration in patients receiving GM-CSF. These data indicate that hematopoietic growth factors like GM-CSF in particular may provide a new perspective in the treatment of acute myeloid leukemia with the possibility of reducing treatment associated mortality and perhaps of increasing the efficacy of antileukemic treatment.
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PMID:New perspectives in the treatment of acute myeloid leukemia by hematopoietic growth factors. 752 49

The long-term results of postremission chemotherapy for 122 consecutive, unselected adults (15-65 years) with acute myeloid leukemia (AML) were assessed in two sequential prospective studies involving an identical 3/7-type induction regimen, and in those achieving remission, another course for early consolidation using 1 day of daunorubicin instead of three. Forty-one patients reaching C.R. during the first study period, were treated with an intensive ablative maintenance ("IM") program for a period of 9 months. They were randomized to either 6 cycles of induction-type regimen or to 6 cycles of an alternating-type regimen consisting of high-dose (HD)-Ara C/AMSA or 5-azacytidine/AMSA every 6 weeks. There was no difference in disease-free survival (DFS) or survival. Results are compared with 27 patients reaching C.R. on the subsequent protocol where IM was replaced by intensive, short-term consolidation ("IC") using 1 cycle of intermediate-dose Ara C plus AMSA and 1 cycle of HD-AraC/AMSA. Fifteen patients received both courses of IC as scheduled, 12 refused the second cycle. There was no significant difference in DFS or survival. Seventeen out of the 122 patients refused either IM or IC following early consolidation ("refusals"). They received no further treatment and served as control. Fourteen percent of all patients underwent autologous or allogeneic bone marrow transplantation (BMT) at different stages of their disease, equally distributed amongst the IM and IC-group. Median DFS was 3.3 months in the refusal group, 12.4 months in the IM-group, and 18.4 months in the IC-group when censored for BMT (p = 0.01) with 6%, 12%, and 40% in C.C.R. at 50 months. Accordingly, median survival was 5.4, 20 and 47 months (p = 0.001) with 6%, 15%, and 45% of patients alive at 5 years. There was a definite trend (p = 0.14) for a higher proportion of long-term survivors in the IM-group when BMT was performed (not censored), while long-term survival was identical in the IC-group whether BMT was considered for analyses (not censored) or not (censored). Median follow-up for both studies is 5.6 years, the longest, 10 years. In conclusion, progressive increments in the intensity of postremission therapy yields in a graded, significant improvement of remission duration and survival.
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PMID:Long-term outcome of postremission chemotherapy for adults with acute myeloid leukemia using different dose-intensities. 753 60

A 70-year-old male was admitted to our hospital because of leukocytosis. The laboratory examination revealed leukocytosis (44,500/microliters) with blasts (99%) in the peripheral blood. Myeloperoxidase staining of the leukemia cells was negative, but the surface phenotype was CD13- and CD33-positive, and negative for all lymphoid antigens. Peroxidase staining using the electron microscope was positive. Thus, the patient was diagnosed as acute myeloblastic leukemia (M0), according to the FAB classification. Although the therapy regimens commonly used for ANLL were effective for some cases with M0, the regimens mainly for ALL were more effective for the others. Thus we cannot determine what is the most effective regimen for M0. Since the patient had many complications, he was treated with low-dose AraC instead of combination chemotherapy. After the beginning of treatment, he became febrile and we added G-CSF to Ara-C. One month later, the patient achieved complete remission without severe infection. After four courses of consolidation therapy, the patient was discharged. He has been maintained in remission for more than 3 years and 8 months with only 5-day oral administration of cytarabine ocfosfate every four weeks.
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PMID:[Continuation of complete remission by oral administration of cytarabine ocfosfate in a patient with M0, who achieved remission by small doses of cytosine arabinoside with G-CSF]. 753 75

We evaluated the efficacy of continuous drip infusion therapy with low dose cytosine arabinoside (AraC) and etoposide (VP16) in poor-condition patients with acute myelogenous leukemia (AML). Patients' age ranged from 19 to 85 years with a median of 63 years. Principally they received continuous drip infusion for 14 days with AraC (20 mg/day) and VP16 (50 mg/day). Complete remission (CR) rate was 58.3% (7/12) in untreated cases, 33.3% (2/6) in refractory cases to the standard chemotherapy, and 28.6% (2/7) in relapsed cases. The duration of CR ranged from 1.5 to 20 (+) months (median 8) in untreated group and from 2 to 22 months (median 10) in refractory and relapsed groups. Adverse effects such as gastroenterological symptoms appeared but were tolerable. Although infections due to myelosuppression appeared in 22 of 25 cases, they were well controlled by antibiotics. Chemotherapy-related death was not observed. Although CR rate and CR duration of this therapy were not sufficiently high, the regimen was effective in some patients with refractory or relapsed AML. Further studies are required to establish the efficacy, indication and safety of this treatment.
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PMID:[Continuous infusion therapy with low dose cytosine arabinoside and etoposide in acute myelogenous leukemia patients hardly tolerable for intensive combination chemotherapy]. 756 93


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