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)

Clonogenic cells from 41 children with newly diagnosed acute myeloid leukemia (AML) were tested in vitro for their sensitivity to cytarabine (Ara-C) and daunorubicin (DNR). The findings were then compared with the patients' responses to induction chemotherapy that uniformly included Ara-C and DNR. Light-density marrow cells were incubated with either or both drugs for one hour and cultured over leukocyte feeder layers; clusters and colonies were scored on days 7, 10, and 14. Only the percentage of cell kill in the presence of 1.8 mumol/L DNR was significantly associated with responses to induction therapy: median of 45% (range, 0% to 98%) for patients achieving complete remission v 16% (range, 4% to 23%) for nonresponders (P = .007). The relationship between clonogenic cell kill less than or equal to 23% and clinical responses was striking. Of the 11 evaluable patients with in vitro findings in this category, ten either failed induction therapy or relapsed within 1 year after attaining remission. Kaplan-Meier analysis of relapse-free survival times indicated longer durations of remission for patients whose blast cells showed increased sensitivity in vitro to Ara-C alone, DNR alone, or a combination of the two agents. Seven of 11 patients with cell kills of greater than or equal to 49% in the presence of 1.25 mumol/L Ara-C remain free of leukemia, compared with only one of 12 whose cells were less sensitive to the drug (P = .006). We conclude that the in vitro sensitivity of clonogenic leukemic progenitors to DNR and Ara-C correlates with treatment outcome in children with newly diagnosed AML.
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PMID:Correlation of drug sensitivity in vitro with clinical responses in childhood acute myeloid leukemia. 346 Jun 47

Normalization of granulocyte counts was obtained with low-dose cytosine arabinoside (Ara-C) in a patient with acute myelogenous leukemia (AML, FAB-M2) who had relapsed on maintenance therapy containing conventional doses of Ara-C and was clinically resistant to high-dose Ara-C treatment. The patient's leukemic cells exhibited an abnormal karyotype (45, X-Y, t[8q; 21q]). To determine whether the response to low-dose Ara-C was a result of induced leukemic cell differentiation, the mature peripheral blood granulocytes were isolated and fused with mitotic chinese hamster ovary (CHO) cells to induce premature chromosome condensation. Karyotypic evaluation of the granulocyte prematurely condensed chromosomes (PCC) during response to low-dose Ara-C demonstrated the presence of cells with 45 chromosomes. This result strongly suggests that part of this patient's response to low-dose Ara-C was a result of induced maturation of the leukemic clone.
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PMID:Induction of differentiation in human myeloid leukemia cells with cytosine arabinoside. 346 37

Forty-one previously untreated patients with a diagnosis of acute myelogenous leukemia (AML) were entered on a study using early intensification followed by a short-term maintenance chemotherapy. Induction and early intensification consisted of three to four cycles of doxorubicin, vincristine, cytosine arabinoside (Ara-C) and prednisone (ADOAP) in escalating dosages. Maintenance therapy used three cycles of Ara-C thioguanine (AT), followed by three cycles of cyclophosphamide and rubidazone with vincristine and prednisone (CROP). Median total duration of therapy was 9 months. The overall complete remission (CR) rate was 73%. Tolerance to chemotherapy and dose escalation were better for patients who received their induction and early intensification in the protected environment. The overall median survival was 75 weeks. Compared to a historical control group treated with long-term maintenance chemotherapy, patients achieving CR on the current study had similar median remission (52 versus 65 weeks; P = 0.3) and survival durations (94 versus 98 weeks). This regimen using early intensification and short-term maintenance chemotherapy did not improve the overall prognosis of this AML population.
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PMID:Early intensification and short-term maintenance chemotherapy does not prolong survival in acute myelogenous leukemia. 346 90

Thirty-eight patients with acute myeloid leukemia (AML) were treated with mitoxantrone (Mto) combined with cytarabine (Ara-C). Five patients had received no previous treatment for acute myeloid leukemia, seven were refractory to treatment with standard first-line chemotherapy, eight had relapsed during treatment, and 18 had relapsed after treatment was stopped. Eleven of these relapses were early (within 6 months of stopping treatment). Mto was given for 5 days by iv bolus injection at a dose of 10 mg/m2 to 12 patients and at 12 mg/m2 to 26. Ara-C was given at a dose of 1 g/m2 twice daily by a 2-hour infusion for 3 days to 37 patients. One patient received Ara-C at a dose of 500 mg/m2 twice daily for 3 days. Toxicity was acceptable except for cerebellar toxicity in two patients, which was irreversible in one. Twenty-two patients (56%) achieved complete remission (CR), and four achieved partial remission (10%). Seventy-five percent of the patients who had relapsed during treatment and 58% of those who had relapsed after treatment was stopped achieved CR. Eleven patients remain in CR at a median time of 10 months (range, 3-17) after treatment. In five patients remissions have lasted greater than 1 year, one in a patient treated in second relapse and one in a patient treated in third relapse. Mto and Ara-C appear to be effective salvage therapy in acute myeloid leukemia and should be considered for incorporation into first-line induction regimens.
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PMID:Phase II study of mitoxantrone and cytarabine in acute myeloid leukemia. 346 43

In a clinical phase I/II study, high-dose cytosine arabinoside and mitoxantrone (HAM) were given in combination to 40 patients with refractory acute myeloid leukemia. All patients had received a 9-day combination of thioguanine, Ara-C, and daunorubicin (TAD-9) as standardized first-line treatment. Refractoriness was defined as (a) nonresponse against two TAD-9 induction cycles, (b) early relapse within the first 6 months on monthly maintenance or after TAD-9 consolidation, (c) relapse after 6 months with nonresponse against one additional TAD-9 cycle, and (d) second and subsequent relapses after successful TAD-9 therapy at the preceding relapse. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours on days 1 through 4; mitoxantrone was started at 12 mg/m2/day on days 3, 4, and 5 and was escalated to 4 and 5 doses of 10 mg/m2/day on days 2 through 5 and 2 through 6. Of the 40 patients, 21 achieved a complete remission (53%), 1 patient had a partial remission, and 5 patients were nonresponders. Thirteen patients died in aplasia due to infections (n = 11), pericardiac effusion, or acute cardiomyopathy. Nonhematologic side effects consisted predominantly of nausea and vomiting, mucositis, and diarrhea. Central nervous system (CNS) symptoms were observed during six treatment courses. Recovery of blood counts occurred at a median of 27 days from the onset of treatment; the median time to complete remission was 36 days. Two of the 21 responders underwent successful bone marrow transplantations. The median remission duration for the remaining 19 patients is 4.5 months, and the median survival time is 9 months. These data emphasize that HAM has high antileukemic activity in refractory AML and strongly suggest starting the combination at earlier stages in AML therapy.
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PMID:High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia. 346 2

A 79-year-old patient with acute myeloblastic leukemia (M2 type in FAB), who has survived more than 5 years, is reported. She was admitted because of fever and anemia. Her white blood cell count was 6200/mm3 with 58% blasts. Bone marrow aspiration showed a nucleated cell count of 26 X 10(4)/mm with 84% blasts, Complete remission was achieved within one month by DCMP two-step method therapy. She relapsed in the third and fifth years after initial therapy. Because leukemic change is atypical, she was treated with a low dose of Ara-C therapy, resulting in complete remission. In cases of acute myelobastic leukemia in elderly patients, long-term survival is rare. However in this case, follow-up has succeeded for 5 years. This patient is the oldest case of acute myeloblastic leukemia ever reported in Japan.
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PMID:[Long-term survival in an elderly patient with acute myeloblastic leukemia]. 347 33

Four patients with acute myeloid leukemia (AML) and three with myelodysplastic syndrome (MDS) were given low dose cytosine arabinoside (Ara-C) therapy. One patient with de novo AML and two patients having refractory anemia with excess of blasts (RAEB) achieved responses. Although the responses lasted for only a short duration (2-3 months), the therapy was well tolerated and not accompanied by severe complications, while severe cytopenia was a frequent side effect with transfusions being necessary in most patients. This therapy could be clinically effective for certain types of AML and MDS (especially RAEB and RAEB in transformation).
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PMID:Low dose cytosine arabinoside therapy in myelodysplastic syndrome and acute myeloid leukemia. 347 89

Fifteen patients with acute myeloid leukaemia were given a total of 17 courses of high-dose cytosine arabinoside (Ara-C). The median age of the patients was 37 years. Four patients developed severe irreversible neurotoxicity, three developed mild to moderate, reversible neurotoxicity, whereas eight patients had no toxicity. Of five patients over the age of 55 years given high dose Ara-C, four developed severe, irreversible neurotoxicity, but there were no severe episodes in nine patients aged 55 years or less. (P less than 0.01). At a dose of 3 g/m2 given intravenously every 12 hours for 3 days, three cases of severe irreversible neurotoxicity were noted in elderly patients. Neurotoxicity at this total dose has previously been considered unusual. Administration of high dose Ara-C at total doses of 18 g/m2 and over carries a risk of severe irreversible cerebellar toxicity that increases with age.
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PMID:The neurotoxicity of high-dose cytosine arabinoside is age-related. 347 81

One hundred thirty-three children with acute myelogenous leukemia (AML) entered the multicenter Pediatric Branch of the Italian Association Against Leukemia trial AIEOP/LAM 8204 between July 1982 and May 1986. Induction therapy consisted of two courses of daunomycin (DNM) plus cytosine arabinoside (Ara-C). Those patients who achieved remission were given four courses of consolidation with DNM, 6-thioguanine (6-TG) and escalated doses of Ara-C followed by six courses of sequential continuation therapy using monthly pairs: etoposide (VP-16)/Ara-C, Ara-C/6-TG, and DNM/Ara-C. Periodic intrathecal Ara-C was used for CNS prophylaxis. One hundred seven (80%) children achieved complete remission (CR). Kaplan-Meier estimates of 3-year disease-free survival (DFS) and event-free survival (EFS) are 41% and 33%, respectively. Relapses occurred in 34 patients after 5 to 97 weeks (32 marrow; 2 marrow plus CNS). Overall, 14 patients died of complications during treatment (nine during induction; five during the postremission phase), mostly from infection. Risk factor analysis showed that induction failures occurred predominantly in children with French-American-British (FAB) M5 and in those with elevated leukocyte counts; by step-up Cox analysis, only FAB subtype was predictive of remission success. None of the variables examined was significant for predicting the duration of remission. Hyperleukocytosis was predictive of a significantly worse EFS rate. These results are encouraging and further support the use of intensive chemotherapy programs for childhood AML.
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PMID:Treatment of acute myelogenous leukemia in children: results of the Italian Cooperative Study AIEOP/LAM 8204. 347 89

The validity of an in vitro clonogenic drug sensitivity assay to predict the induction and the duration of complete remission was evaluated in a group of 81 patients with acute myelogenous leukemia treated with chemotherapy including an anthracycline drug (daunorubicin or adriamycin) and cytosine arabinoside (Ara-C). The inhibition of bone marrow clonogenic leukemic cells by in vitro exposure to anthracyclines 10(-5) and 10(-6) M, Ara-C 10(-5) M, and daunorubicin 10(-6) M + Ara-C 10(-7) M was significantly correlated with the achievement of a complete remission, but not with the duration of remission. A high second plating efficiency was correlated with short duration of complete remission, reflecting the poor prognosis of a high self-renewal capacity.
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PMID:Prognostic value of clonogenic assay for induction and duration of complete remission in acute myelogenous leukemia. 347 35


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