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)

An efficiency of the acute myeloblastic leukemia therapy has been assessed in 79 patients aged over 60 years. Twenty six patients out of this group have been treated with usual or reduced doses of doxorubicin and cytarabine (ADR-Ara-C) 35--low doses of cytarabine (LD Ara-C), 11-6-mercaptopurine (6 MP), and 7 patients died before chemotherapy. Complete remission in group treated with ADR-Ara-C was achieved in 23% of patients while partial remission in 42%. Median survival in this group was 5.8 months (range from 0.5 to 16 months). Percentage of the complete remissions in the group treated with LD-Ara-C was 6%, and partial remissions 40%. Median survival was 4.7 months (range from 0.5 to 14.2 months). Partial remission in 5 out of 11 patients treated with 6 MP (36%) and no complete remissions were noted. Median survival was 3.9 months. Therapy with ADR-Ara-C produced marked leucopenia and thrombocytopenia in the majority of treated patients. Vomiting, hemorrhagic complications, and bacterial infections have also been noted. These adverse reactions have been less frequent in patients treated with LD-Ara-C, and 6 MP. Ten patients (38%) treated with ADR-Ara-C and 7 patients treated with LD-Ara-C died during remission inducing therapy.
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PMID:[Results of treating acute myeloblastic leukemia in patients over 60 years of age]. 184 11

We have examined the effect of recombinant interleukin 3 (rIL-3) on the metabolism of high-dose cytosine arabinoside (Ara-C), an S-phase-specific agent, in normal human bone marrow mononuclear cells (BMMC) and leukemic blasts from patients with acute myeloid leukemia (AML). Exposure to rIL-3 for 24 h significantly increased the percentage of cycling S-phase cells in normal BMMC as well as leukemic cells. A concomitant expansion of intracellular deoxycytidine triphosphate (dCTP) levels occurred to a significantly greater extent in normal BMMC. Compared to treatment with Ara-C (10 mumol/liter) alone, prior and coadministration of rIL-3 with Ara-C increased Ara-CTP levels in leukemic blasts. However, an identical treatment produced significantly higher dCTP levels in normal BMMC, resulting in a significantly lower mean Ara-CTP to dCTP pool ratio in normal BMMC compared to that observed in each of the samples of AML blasts. Following treatment with Ara-C plus rIL-3 versus Ara-C alone, the alteration in Ara-C DNA incorporation corresponded with the change in Ara-CTP to dCTP ratio observed in normal BMMC and AML blasts. The differential effect of rIL-3 on the metabolism of high-dose Ara-C in normal versus leukemic cells may indicate a role for rIL-3 in enhancing the selectivity of Ara-C toward leukemic myeloblasts.
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PMID:Differential effect of interleukin 3 on the metabolism of high-dose cytosine arabinoside in normal versus leukemic human bone marrow cells. 189 53

The New Zealand Acute Myeloid Leukaemia (AML-1) study ran from 1985 to 1988. Ninety-two patients with acute myeloid leukaemia between the ages of 13-65 were entered. Remission induction treatment consisted of cytosine arabinoside (Ara-C) 100 mg/m2 12 hourly for seven days and daunorubicin (DNR) 45 mg/m2 daily for three days. Fifty-six patients entered remission (61%). The patients were randomised at diagnosis to receive either three further courses of Ara-C (five days) and DNR (two days) in the same dosage or three courses of VP16 100 mg/m2 daily for five days and one dose of mAMSA of 200 mg/m2 as postremission consolidation. No difference in survival between these two consolidation treatments was seen (p = 0.96). The overall survival of the original 92 patients is 13% with a minimum follow up of two and a half years. However, for those patients solely treated with the trial protocol, disease free survival at 2% is poor. The poor long term results could reflect the relatively low intensity consolidation treatment used in this study. However, since a majority of patients presenting in New Zealand with acute myeloid leukaemia between these ages were entered into the trial, the results could also reflect the relative lack of selection bias which affects many published studies of acute leukaemia treatment.
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PMID:Acute myeloid leukaemia: results of the New Zealand AML-1 study. The Leukaemia Study Group of the New Zealand Society for Haematology. 192 3

A controlled study was conducted to evaluate the efficacy of high-dose cytosine arabinoside (Ara-C) in consolidation therapy of acute nonlymphocytic leukemia in remission. Twenty-seven patients with acute nonlymphocytic leukemia during their first complete remission were divided into two groups. The high-dose Ara-C group (15 patients) received two courses of high-dose Ara-C and daunorubicin, i.e., 3 g/m2 of Ara-C IV over 1 h every 12 h eight times followed by 25 mg/m2 per day daunorubicin IV bolus for 2 days, and no maintenance chemotherapy. The control group (12 patients) received the conventional consolidation therapy (usually 7 days administration of 200 mg/m2 of behenoyl-arabino-furanosylcytosine and 2 to 3 days administration of 25 mg/m2 of daunorubicin) repeated every 3 to 4 months for more than 2 years. There were no significant differences in the duration of remission and survival between the two groups. It is suggested that high-dose Ara-C consolidation is worth employing in the treatment of acute nonlymphocytic leukemia because of its convenience for patients.
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PMID:High-dose cytosine arabinoside as consolidation chemotherapy for acute nonlymphocytic leukemia in remission. 195 54

Based on in vitro data suggesting that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is capable of stimulating acute myeloid leukemia (AML) blast cells to become more sensitive to cell-cycle-specific drugs we conducted a phase I/II study in de novo AML patients (pts). rhGM-CSF (250 micrograms/m2/d, continuous intravenous infusion) was administered in 18 pts suffering from de novo AML in combination with standard induction chemotherapy (3 + 7 = daunorubicin 45 mg/m2 days 1 through 3, cytosine-arabinoside [Ara-C] 200 mg/m2 continuous infusion days 1 through 7). GM-CSF was started 48 or 24 hours before chemotherapy (prephase) in 14 pts. In four pts with high white blood cell counts (WBC) rhGM-CSF was started after chemotherapy-induced cell reduction (WBC less than 30,000/mm3). During prephase GM-CSF induced an increase in neutrophil and blast cell counts in 13 of 14 and 10 of 14 pts, respectively. In vivo recruitment of leukemic cells into drug-sensitive phases of the cell cycle could be demonstrated by multiparameter cell-cycle analyses in peripheral blood (n = 7) and bone marrow (n = 4) specimens. On day 14, complete aplasia was evident in 17 of 18 pts. GM-CSF was administered until recovery from chemotherapy-induced myelosuppression (absolute neutrophil counts, [ANC] greater than 500/mm3). Fifteen pts (83%) achieved complete remission, 12 did so with one cycle. A shorter duration of neutropenia was evident in these pts compared with historical controls (n = 39), (ANC greater than 500/mm3, day 22.5 +/- 3.4 v 25.2 +/- 3.7, P less than .05). Three pts achieved complete remission after a second cycle (same combination of rhGM-CSF and 3 + 7). Two pts died during bone marrow aplasia because of invasive pulmonary aspergillosis. Clinical side effects possibly related to GM-CSF, mainly fever, diarrhea, and weight gain were mild and tolerable (World Health Organization toxicity grade less than or equal to 2). Together, rhGM-CSF recruits kinetically quiescient AML cells in vivo to enter drug-sensitive phases of the cell cycle and promotes early myeloid recovery from aplasia after exposure to standard induction chemotherapy for AML.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in de novo acute myeloid leukemia. 199 13

4'-Demethoxydaunorubicin (idarubicin [IDR]) is a new anthracycline that differs from its parent compound by the deletion of a methoxy group at position 4 of the chromophore ring. This minor structural modification results in a more lipophilic compound with a unique metabolite that has a prolonged plasma half-life as well as in vitro and in vivo antileukemia activity. To determine its activity in acute myelogenous leukemia (AML), 130 consecutive adult patients between the ages of 16 and 60 with newly diagnosed disease were randomized in a single institution study to receive either IDR in combination with cytosine arabinoside (Ara-C) or standard therapy with daunorubicin (DNR) and Ara-C. The trial was analyzed using the O'Brien-Fleming multiple testing design that allowed for periodic inspection of the data at specific patient accession points. After accrual of 60 patients per arm, analysis showed that patients who received IDR/Ara-C had a superior response compared with those who received standard therapy: 48 of 60 patients (80%) achieved complete remission on the former arm compared with 35 of 60 patients on the latter (58%, P = .005). Logistic regression analysis of factors associated with complete response indicated that treatment with IDR/Ara-C offered a significant advantage to patients who presented with a high initial white blood cell count compared with treatment with DNR/Ara-C. The degree of marrow aplasia was approximately the same on each arm as was nonhematologic toxicity. Overall survival for patients on the IDR/Ara-C arm was 19.5 months compared with 13.5 months on the DNR/Ara-C arm (P = .025) at a median follow-up of 2.5 years. We conclude that IDR/Ara-C can effectively replace standard therapy with DNR/Ara-C in adult patients less than age 60 with newly diagnosed AML.
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PMID:Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. 201 95

With the aim of improving the treatment of AML patients the activities of selected nucleoside metabolizing enzymes of possible implication for the initial metabolism of Ara-C have been studied in leukemic and normal cells. An increased ADA activity, a slightly changed PNP activity, a decreased CDD activity and an increased dCK activity, including deviation in substrate specificity, were found in myeloid leukemic cells. The increase of ADA may in part be related to immaturity of the cells. This is supported by the finding of a decrease in the ADA activity during experimental induced differentiation of myeloid cells. On the other hand differentiation is not dependent on the ADA decrease, since differentiation can occur without the decrease of ADA. The correlation between myeloid blast counts in peripheral blood from AML patients and the ADA activity also supports the connection between the development stage of the cells and the ADA activity. Minor changes of the ADA activity in myeloid cells from patients with liver cirrhosis have been observed without changes in the maturity of the cells indicating that other factors than the differentiation of the cells are of importance for the activity of ADA in myeloid cells. Only minor changes have been observed in the activity of PNP related to myeloid leukemic cells. CDD activity is decreased in myeloid leukemic cells. Differentiation is probably of major importance for the activity, experimentally supported by the increase observed concurrently with induced differentiation of myeloid cells. An inverse correlation between the CDD activity and the blast counts in patients with AML is also supportive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Features of the initial metabolism of 1-beta-D-arabinofuranosylcytosine in human myeloid leukemic cells. 202 53

Forty-eight patients with acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes (MDS) were treated with low-dose Ara-C regimen (LDAC) (10 mg/m2 or 10 mg/body subcutaneously every 12 hours). Complete remission (CR) was obtained in sixteen patients (33%) and partial remission (PR) in six (16%). Seven of eight patients with hypoplastic leukemia entered CR. However, LDAC was not effective in MDS and ANLL developing from MDS. The rate of CR was 20% in relapsed or refractory ANLL. Relapse was occurred in thirteen patients until now. The median duration of remission was 7 months (range: 3-20 months). Seven of the sixteen patients who achieved CR were received LDAC at the same dose for 10 days every month as a maintenance therapy. The duration of CR of these patients was shown to be longer than that of the patients without any maintenance therapy. Myelosuppression was observed in nearly all of them and the other clinical findings including cytogenetic analysis indicated cytotoxicity rather than differentiation as the mechanism of LDAC. LDAC was effective especially in hypoplastic leukemia and the maintenance therapy was found to prolong the duration of CR.
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PMID:[Clinical effects of low-dose Ara-C in acute nonlymphocytic leukemia and myelodysplastic syndromes]. 202 36

Cytosine arabinoside (AraC) is one of the most active drugs in the treatment of acute leukemias and is widely applied at all phases of therapy. In spite of extensive clinical and experimental investigations, its intracellular metabolism and especially its mechanism of action are still not fully elucidated. Controversy also continues about the most appropriate way and dose of administration; which differs by more than 100 fold in clinical studies ranging from low-dose, over standard and intermediate dose regimens, to high-dose protocols. The present review is focused on the role and place of high-dose AraC treatment in acute myeloid leukemia (AML). Based on available clinical and experimental data, the following conclusions can be drawn: Not considering possible but not yet demonstrated beneficial long-term effects, the incorporation of high-dose AraC into induction therapy has not resulted in an improvement of overall remission rate, with the possible exception of patients with slow initial cytoreduction after a first course of conventional treatment. Promising results, however, emerge from high-dose AraC-based consolidation protocols, which need confirmation in prospectively randomized comparative trials. In relapsed and refractory AML, higher than conventional doses undoubtedly enhance the efficacy of AraC salvage therapy. The question of whether the antileukemic activity of intermediate-dose regimens with 500-1,000 mg/m2 AraC is equivalent to that of high-dose protocols applying 2,000-3,000 mg/m2 AraC, however, remains open but may soon be answered by ongoing controlled clinical and pharmacologic investigations.
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PMID:Cytosine arabinoside in the treatment of acute myeloid leukemia: the role and place of high-dose regimens. 203 74

In June 1984, the Pediatric Oncology Group (POG) initiated a pilot study (8498) using high-dose cytarabine (HdA; 3 g/m2) for intensification of early therapy in childhood acute myelogenous leukemia (AML) (group I). Remission induction therapy consisted of two courses of daunorubicin, cytarabine (Ara-C), and thioguanine (DAT). Postremission therapy consisted of four sequential courses, each consisting of (1) four doses of HdA (HdA4) followed by asparaginase (L-Asp), (2) etoposide (VP) plus azacytidine (Az), (3) prednisone, vincristine, methotrexate, and mercaptopurine (POMP), and (4) Ara-C daily for 5 days by continuous infusion. Six doses of intrathecal Ara-C were given for CNS prophylaxis. In December 1986, the protocol was amended (group II) to substitute six doses of HdA (HdA6) for the second DAT (two + five) induction course; postinduction, a single course of HdA6 was given instead of four HdA/L-Asp courses, and the remainder of the therapy was unchanged. One hundred forty group I patients and 145 group II patients were assessable. The two groups were similar with regard to clinical prognostic groups. No significant differences were noted in the two groups with regard to remission induction (85% [SE = 2%] in each group), induction deaths (6.5% v 7.0%), or deaths in remission (one in each group). Cerebellar toxicity was reported in three patients in group II (with HdA6) but none in group I (HdA4). At present, patients who received HdA6 (group II) had higher event-free survival than patients in group I (EFS at 3 years, 34% [SE = 11%] v 29% [SE = 4%]), and disease-free survival (DFS at 3 years, 42% [SE = 14%] v 34% [SE = 4%]), but the differences were not statistically significant. In both groups, children less than 2 years and those with WBCs less than 100,000/microL had significantly better outcome (EFS of 55% [SE = 10%] and 36% [SE = 5%] at 3 years, respectively) than children greater than or equal to 2 years and those with WBCs greater than or equal to 100,000/microL (EFS of 27% [SE = 5%] and 20% [SE = 9%] at 3 years, respectively.
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PMID:High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: a Pediatric Oncology Group study. 206 54


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