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 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

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

To determine the value of aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis (IPA), we initiated a prospective randomized multicenter trial. The scheduled intent-to-treat interim analysis included 115 patients (30%) with prolonged neutropenia after chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia/high-grade non-Hodgkin's lymphoma, or solid tumors undergoing autologous stem cell transplantation. Sixty-five patients had been randomized to receive prophylactic aerosol amphotericin B inhalations at a dose of 10 mg twice daily (group A); for the remaining 50 patients no aerosol amphotericin B prophylaxis was used (group B). No serious side effects from amphotericin B inhalations occurred, but coughing (54%), bad taste (51%), and nausea (37%) caused early cessation of aerosol amphotericin B prophylaxis in 23% (15/65) of courses. In group A, the incidence of proven, probably, or possible IPA was 5% (3/65) as compared with 12% (6/50) in group B (p > 0.05). Microbiologically documented bacterial pneumonias were observed in 5/65 (8%) patients in group A and in 1/50 (2%) patients in group B (p > 0.05). Thus, no reduction in incidence of IPA from use of prophylactic aerosol amphotericin B inhalations was found in this interim analysis. As there were no serious side effects from aerosol amphotericin B prophylaxis, accrual in the study will continue for a total of 380 patients.
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PMID:Aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in neutropenic cancer patients. 853 60

Patients with AML who relapse after an initial remission, have a poor prognosis. Administration of hemopoietic growth factors (HGFs) such as interleukin-3 (IL-3) during chemotherapy may result in an increased cell kill by cytotoxic agents. In addition, administration of IL-3 following chemotherapy may potentially accelerate hemopoietic recovery from chemotherapy-induced bone marrow hypoplasia. We performed an open labelled, phase I/II study in which patients received IL-3 by continuous infusion from 24 h before the beginning of chemotherapy until day 28. Chemotherapy included daunorubicin or mitoxantrone days 1-3 and cytarabine 200 mg/m2 days 1-7. IL-3 was given at a dose of 5 microgram(s)/kg/day in 10 patients, 7.5 microgram(s)/kg /day in six patients and 10 microgram(s)/kg/day in four patients. Complete remissions (CR) after one cycle of this treatment were obtained in 5/10 patients and 5 microgram(s)/ kg group, 2/6 in the 7.5 microgram(s)/kg group and 3/4 in the 10 microgram(s)/kg group). Thus, 50% (10/20) of all individuals and 45% (5/11) of the elderly patients attained CR. Eight of 20 patients entered PR, and 2/20 patients died during the hypoplastic phase from infectious complications. Neutrophils and platelets recovered to 0.5 x 10(9)/l at day 25 (median) and to 50 x 10(9)/l at day 32, respectively. Adverse events during IL-3 and concomitant chemotherapy were fluid retention (4/20), rash (14/20), bone pain (2/20), headache (10/20), chest pain (1/20), arthritis (1/20), fever and nausea. IL-3 (at the dose of 10 microgram(s)/kg) was discontinued in two patients because of side-effects (fluid retention, fever, rash and chest pain), and in two other patients the high IL-3 dose was tolerated with no problems for 29 days. Thus, IL-3 applied to patients with high-risk AML at dosages of 5-10 microgram(s)/kg is tolerated with acceptable toxicity and results in a satisfactory frequency of complete responses following a single treatment cycle.
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PMID:Recombinant human interleukin-3 (rH IL-3) in combination with remission induction chemotherapy in patients with relapsed acute myelogenous leukemia (AML): a phase I/II study. 855 36

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

This report describes the results of induction chemotherapy with idarubicin (IDA) plus N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), a newly designed induction regimen, in cases of previously untreated acute myelogenous leukemia (AML). The study was conducted by the Multicenter Clinical Study Group of the Korean Biologic Response Modifier Society (KBRMS). From March 1994 through January 1995, 40 patients were treated. The median age was 30 years (range, 15 months to 65 years), with a distribution according to the French-American-British (FAB) classification of one MO, nine MI, 15 M2, six M3, four M4, and five M5 patients. Remission induction therapy consisted of IDA 12 mg/m2 intravenously (i.v.) over 30 minutes daily on days 1 to 3, in combination with BH-AC 300 mg/m2 over 4 hours daily on days 1 to 7 (in patients aged 41 to 65 years, BH-AC dosage was decreased to 200 mg/m2/d). Complete remission (CR) was achieved in 30 patients (75%), 22 by the first induction therapy and eight by the second induction therapy. Ten patients (25%) failed to respond to therapy, six due to resistant disease and four due to death caused by aplasia. The time to CR was 30 days, the median granulocytopenic period was 19 days, and the thrombocytopenic period was 24 days. All nonhematologic side effects such as nausea, vomiting, mucositis, skin eruption, liver and cardiac dysfunction, and neurotoxicity, were transient and tolerable. These data indicate an efficacy comparable to that of other combinations of IDA (or other anthracyclines) with cytosine arabinoside (Ara-C) for remission induction in AML.
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PMID:Induction chemotherapy with idarubicin plus N4-behenoyl-1-beta-D-arabinofuranosylcytosine in acute myelogenous leukemia: a newly designed induction regimen--a prospective, cooperative multicenter study. 891 13

We have retrospectively reviewed the ability to safely deliver total body irradiation (TBI) in the outpatient setting in 10 pediatric patients undergoing stem cell transplantation. Patients had a median age of 14 years (range 9-17 years) with diagnoses that included ALL in second remission, AML in second remission, myelodysplastic syndrome, Ewing's sarcoma, and rhabdomyosarcoma. Patients received a total of 1375 cGy or 1440 cGy given in a hyperfractionated schedule (11 or 12 fractions) over a 4-day period. All children were seen in the outpatient clinic daily during TBI and all were housed within a 20 mile radius of our institution during this period. Eight patients achieved good control of nausea and emesis with ondansetron alone while two patients required ondansetron and diphenhydramine. Nine patients received some form of intravenous hydration during this period (hyperalimentation, fluid boluses in clinic, or night-time intravenous fluids). One patient maintained good hydration with oral intake alone. Only one child required admission during this period for persistent nausea and vomiting despite antiemetics and intravenous fluids. A cost approximation suggests that TBI delivered in the outpatient setting resulted in a saving of approximately $2400 per patient. We conclude that TBI administered to children and adolescents in the outpatient setting can be a safe and cost-effective practice.
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PMID:Outpatient total body irradiation for pediatric patients undergoing stem cell transplantation. 919 47

2-Chlorodeoxyadenosine (2-CdA) is a purine analogue which has proved to be active in acute myeloid leukemia (AML), especially in children. In adults, results yielded by 2-CdA alone or with ara-C were less encouraging. Here we report on the efficacy of 2-CdA with or without daunorubicin (DNR) in 19 relapsing or refractory adult AML patients, with a median age of 57 years. 2-CdA was administered as a continuous infusion to all patients at a dose of 0.1 mg/kg per day for 7 days. For 14 patients, DNR was added at a dose of 50 mg/m2 per day on days 5, 6, and 7. Antileukemic activity was observed in all the patients, but no single complete remission was achieved. One patient had a long-lasting partial response (response rate=5%). The remaining patients died of progressive AML (n=7), uncontrollable infection with persistent disease (n=10), and cerebral hemorrhage (n=1). Median survival from start of 2-CdA therapy was 56 days. Long-lasting neutropenia and transfusion-dependent thrombopenia were encountered in all 16 evaluable patients. Grade 4 hepatic toxicity occurred in one patient. Other side effects included nausea in six, mucositis in three, and mental disturbances in three patients. Compared with 2-CdA alone, the addition of DNR to 2-CdA changed neither the response rate nor the toxicities. In conclusion, our data do not support the use of 2-CdA +/- DNR for relapsing or refractory adult AML patients, at least as used in the present regimen.
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PMID:2-Chlorodeoxyadenosine with or without daunorubicin in relapsed or refractory acute myeloid leukemia. 948 20


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