Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 77-year-old female with left hemiplegia caused by cerebral infarction and with mild senile dementia was admitted for further examination of hematological abnormalities. She was diagnosed as acute myelogenous leukemia (AML-M5a) according to French-American-British classification. Since intensive combination chemotherapy seemed difficult, she was treated with oral administration of cytarabine ocfosfate (200 mg/day, for 14 days), a cytidine deaminase-resistant derivative of Ara-C, resulting in complete remission. Major side effects were nausea, vomiting and appetite loss, but their incidences were reduced tolerably when cytarabine ocfosfate was given just before sleeping. Cytarabine ocfosfate might be useful to treat AML in elderly patients having certain complications such as cerebrovascular disease.
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PMID:[Successful treatment of acute myelogenous leukemia in an elderly patient with cytarabine ocfosfate]. 812 96

Five children with AML were treated with high-doses of Ara-C (2 g/m2) during consolidation. After 17 cycles the toxicity was evaluated. Granulocytopenia (< 0.5 x 10(9)/l) and thrombocytopenia (< 25 x 10(9)/l) were stated after 15/17 and 13/17 cycles respectively. The nadir of bone marrow suppression appeared between day 10 and 14. In one case treatment related death during severe myelosuppression was noted. In individual cases jaundice with elevated activity of aminotransferases, paralytic ileus and pulmonary oedema were observed. All these adverse reactions were reversible. Other toxicities such as nausea/vomiting, stomatitis, diarrhea, infections and drug related fever were transient. No neurologic toxicity was seen. There is a need for developing a new way of the administration of high-dose Ara-C which could substantially reduce toxicity of the drug.
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PMID:[Preliminary evaluation of adverse effects after administration of arabinoside cytosine (Ara-C) in high doses to children with acute myelogenous leukemia]. 820 12

A nationwide multi-center cooperative phase II clinical study of irinotecan hydrochloride (CPT-11) was conducted to evaluate its efficacy in intractable malignant lymphoma and acute leukemia. In malignant lymphoma, one course of CPT-11 consisted of intravenous drip infusion at a dose of 40 mg/m2 once daily for 3 consecutive days, performed once a week. In acute leukemia, one course of CPT-11 consisted of intravenous drip infusion at a dose of 15 to 20 mg/m2 a day twice daily for 7 consecutive days (1 cycle), performed every 2 to 4 weeks. Among the 79 patients with malignant lymphoma and 50 patients with acute leukemia enrolled in the study, 66 and 41 patients, respectively, completed treatment. These patients had all undergone chemotherapy prior to treatment. Among the malignant lymphomas, the response rate in non-Hodgkin's lymphoma (NHL), including 9 CRs, was 42% (26/62, 95% CI: 30-54%); of these there was a response rate of 39% (5/13), including 1 CR, in adult T-cell leukemia (ATL) as well. In Hodgkin's disease (HD), on the other hand, there were no cases in which efficacy was demonstrated (0/4). The overall response rate in malignant lymphoma was 39% (26/66), and the response rate even among the recurrent intransigent cases was 42% (16/38). The 50% survival time (MST) in the 74 eligible cases of malignant lymphoma was 153 days. In acute leukemia, on the other hand, partial remission was observed in 2 of 17 cases (12%) of acute lymphocytic leukemia (ALL), but no cases of remission were observed in the 24 patients with acute myelogenous leukemia (AML). The overall remission rate in acute leukemia was 5% (2/41, 95% CI: 1-14%). The principal adverse effects were myelosuppression in malignant lymphoma and gastrointestinal symptoms, including diarrhea, nausea/vomiting, anorexia and abdominal pain, in both malignant lymphoma and acute leukemia, and there was little organ damage to the heart, liver or kidney. Myelosuppression and gastrointestinal adverse effects were severe in some of the patients, so caution is required. Based on the above findings, CPT-11 appears to be efficacious in the treatment of non-Hodgkin's lymphoma.
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PMID:[Late phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies]. 821 Feb 56

An early phase II study of CPT-11 (irinotecan hydrochloride) was conducted in patients with hematological malignancies by 4 administration regimens in a cooperative study involving 13 institutes in Japan. The overall response rate was 23% (7/30) for non-Hodgkin's lymphoma, 33% (1/3) for Hodgkin's disease, 18% (2/11) for acute lymphoblastic leukemia and 7% (1/15) for acute myelogenous leukemia. One PR was also obtained in a patient with chronic myelogenous leukemia. Among responders, 6 relapsed and refractory malignant lymphomas (ML) and 2 relapsed and refractory acute leukemias (AL) were involved. The response rates in ML with the regimens B (40 mg/m2 for 5 days every 3-4 weeks) and C (40 mg/m2 for 3 days every weeks) were 31% (5/16) and 33% (3/9), respectively. The other regimens (regimen A, 200 mg/m2 once a day every 3-4 weeks and regimen D) resulted in no response. Responses in AL were only observed in regimen D (20 mg/m2 twice a day for 7 days every 3-4 weeks). Major toxicities were leukopenia (91%), nausea/vomiting (74%), diarrhea (73%) and anorexia (64%). The incidence of severe gastrointestinal symptoms was higher in regimen B than regimen C. Further studies are warranted to confirm the effectiveness and safety of CPT-11 against ML and AL. The recommended administration schedule was regimen C for ML and regimen D for AL.
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PMID:[An early phase II study of CPT-11 (irinotecan hydrochloride) in patients with hematological malignancies]. 829 18

This manuscript reports Bacillus cereus sepsis in two cases with acute myelogenous leukemia (AML) who suffered complications of fatal intracranial hemorrhage during remission induction therapy. The first case was 43-year-old male with AML (M0) receiving first consolidation chemotherapy who developed sudden diarrhea, abdominal pain and spiking fever. Two days later, he died of intracranial hemorrhage. The second case was 15-year-old male with AML (M5b) who was receiving first induction chemotherapy. He developed headache and vomiting following spiking fever and diarrhea. He died of subarachnoid hemorrhage the next day. In both cases, Bacillus cereus was isolated from blood culture. Fatal intracranial hemorrhage due to severe bleeding tendency caused rapid to death in both cases. These bleeding tendencies might have been induced by B. cereus sepsis. In addition, we should not overlook B. cereus as contamination, but rather consider it as a potential pathogen, when isolated from blood culture.
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PMID:[Two cases of acute myelogenous leukemia with Bacillus cereus bacteremia resulting in fatal intracranial hemorrhage]. 829 31

Ninety-seven patients with refractory or relapsed acute myelogenous leukemia (AML), median age 37 years, received as salvage therapy a single course of idarubicin 6 mg/m2 as an intravenous (i.v.) bolus daily for 5 days, cytarabine (Ara-C) 600 mg/m2 i.v. for a period of 2 hours daily for 5 days and etoposide (VP-16) 150 mg/m2 for a period of 2 hours daily for 3 days (ICE protocol). Thirty-six patients were primarily resistant to standard inductive therapy with daunorubicin and Ara-C; 50 patients were in first relapse, three patients in second or third relapse, and eight patients in relapse after transplants. Forty-two (43%) out of 97 patients achieved complete remission, 11 patients died of infection or hemorrhage during induction, and 44 patients (45%) had resistant disease. Of the various variables examined, only disease status (i.e. refractory versus relapsed AML) was predictive for a significantly lower response rate. The median remission duration was 16 weeks; the overall median survival was 10 weeks. Nausea, vomiting, and oral mucositis were common but were rarely severe. No patient experienced treatment-related cardiac toxicity. In conclusion, the ICE protocol is a tolerable regimen providing effective antileukemic activity in patients with advanced AML. The evolution of this protocol in previously untreated patients with AML appears indicated.
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PMID:Idarubicin in combination with intermediate-dose cytarabine and VP-16 in the treatment of refractory or rapidly relapsed patients with acute myeloid leukemia. The GIMEMA Cooperative Group. 842 73

18 consecutive patients with acute myeloid leukaemia (AML) treated with 34 cycles of intensive chemotherapy received ondansetron as antiemetic treatment. 14 patients were chemotherapy-naive, while 4 patients were treated for relapsed leukaemia. All patients received at least one cycle of chemotherapy, 11 patients (61%) received two cycles and 5 patients (28%) received three cycles. The remission induction regimen consisted of cytarabine 200 mg/m2 daily from day 1 to day 7, in combination with an anthracycline or amsacrine on 3 days. During the second and third cycle the dose of cytarabine was increased. Ondansetron was administered as follows: 8 mg intravenously before the start of chemotherapy, followed by 8 mg orally three times daily for 10 days. 50% of patients had no episodes of vomiting during the first cycle of chemotherapy and 78% had less than five episodes of vomiting over 10 days. 72% of patients had no or only mild nausea. These high response rates were maintained during the subsequent cycles. No side-effects due to ondansetron were registered. These data indicate that ondansetron is efficacious in preventing nausea and vomiting in patients with AML treated with intensive chemotherapy.
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PMID:Control of nausea and vomiting with ondansetron in patients treated with intensive non-cisplatin chemotherapy for acute myeloid leukaemia. 843 1

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), given intravenously 5 micrograms/kg per day, was administered on days 4-8 of timed-sequential chemotherapy (TSC) with mitoxantrone, 12 mg/m2 per day on days 1-3, etoposide, 200 mg/m2 per day on days 8-10 and cytarabine, 500 mg/m2 per day on days 1-3 and 8-10, in 22 patients aged < 60 years with refractory acute myelogenous leukemia in an attempt to increase recruitment of leukemic cells in S phase before the second sequence of TSC. Thirty-eight patients treated with TSC without GM-CSF in a previous trial served as historical controls. In GM-CSF-treated patients, median duration of neutropenia < 0.5 x 10(9)/1 was 33 days and of platelet transfusion requirement 30 days, without any increase by comparison with controls. WHO grade 3 or more extra-hematologic toxicity included sepsis in 60% of patients, vomiting in 30%, diarrhea in 15%, hyper-bilirubinemia in 15%, and mucositis in 10%, without any difference with controls. Among 20 evaluable patients six individuals (30%), with a 95% confidence interval (CI) ranging from 12-54% achieved complete remission, 11 (55%, CI 31-77%) did not respond to therapy and three (15%, CI 3-38%) died from infection. There was no demonstrable in vivo proliferation of leukemic cells during the 5 days of administration of GM-CSF. The average percentage of bone marrow cells in S phase in five patients was 4.0 +/- 2.8 on day 4 and 7.0 +/- 7.2 on day 8 (p = NS). In this cohort of patients refractory to cytarabine, addition of GM-CSF did not increase efficacy of TSC by comparison with historical controls.
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PMID:Granulocyte-macrophage colony-stimulating factor in association to timed-sequential chemotherapy with mitoxantrone, etoposide, and cytarabine for refractory acute myelogenous leukemia. 844 42

High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3-7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7-3-7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5-2-5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC-3-7 and 74% with 7-3-7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3-7 and 12 months with 7-3-7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3-7 and 24% on 7-3-7. Patients in CR tended to survive longer with HIDAC-3-7 but there were no overall survival differences between the two arms. HIDAC-3-7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7-3-7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3-7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC-3-7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.
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PMID:A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. 869 26

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor-risk ALs.
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PMID:Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. 869 37


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