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)

The toxic effects of high-dose busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) with autologous or syngeneic bone marrow rescue were evaluated in 19 patients (11 with acute myelocytic leukemia, one with acute lymphocytic leukemia, one with acute myelofibrosis, two with chronic myelocytic leukemia, one with Hodgkin's disease, and three with non-Hodgkin's lymphoma). Their mean age was 26 years (range, 6-50); nine patients had syngeneic and ten had autologous bone marrow rescue (six of whom had in vitro bone marrow incubation with 4-hydroperoxycyclophosphamide). Severe myelosuppression was expected and was seen in all patients; leukocyte and platelet count recovery occurred at a median of 19 days (range, 11-59) and 30 days (range, 20-89), respectively. Nausea, vomiting, and diarrhea were frequent but readily managed with vigorous medical therapy. Stomatitis was severe in 14 patients. Skin, renal, cardiac, pulmonary, and CNS complications directly attributable to drug-related toxic effects were transient and non-life-threatening. Hepatic function abnormalities were common but tended to be transient. Most patients tolerated high-dose busulfan and cyclophosphamide with manageable side effects. Hepatic veno-occlusive disease was fatal in two patients, while diffuse interstitial pneumonitis with disseminated herpes virus infection was fatal in three patients with lymphoma. All patients treated in relapse or without previous therapy had a complete tumor response. Further studies with this regimen should be pursued.
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PMID:Preliminary results of high-dose busulfan and cyclophosphamide with syngeneic or autologous bone marrow rescue. 637 4

Thirty patients with advanced acute leukemia and lymphoma were treated with the sequential combination of high dose ARA-C (HiDAC 3 gm/m2 infused i.v. over 3 h at 0, 12, 24, 36 h) and asparaginase (ASP 6.000 IU/m2 i.m. at hour 42). The sequence was given on day 1 and 8 irrespective of the degree of myelosuppression. Of 22 patients with leukemia there was only one who was absolutely refractory to therapy. Complete remission was induced in 3 patients with ANLL (30%) and in 3 with ALL (30%). Three patients became hypoplastic but recovered with blasts and 12 died from infection, complicated by intracranial hemorrhage in 3, during hypoplasia. Of 8 patients with lymphoma, 2 were clearly refractory to therapy, one died from sepsis and the remaining 5 all entered remission (2 CR + 3 PR, 62%). Activity of HiDAC/ASP against CNS disease is suggested by the clinical response seen in patients with overt meningeal or intracerebral involvement. Toxicity associated with HiDAC/ASP was mainly hematologic. All but one patient experienced hypoplasia and severe pancytopenia; documented infections and major hemorrhages occurred in 80 and 20% of patients respectively. We conclude that HiDAC/ASP is a regimen with definite activity against acute leukemia and lymphoma including CNS disease. Alternate treatment schedules should be explored in order to reduce marrow toxicity.
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PMID:Sequential combination of high dose ARA-C (HiDAC) and asparaginase (ASP) for the treatment of advanced acute leukemia and lymphoma. 647 2

A phase II pilot study of amsacrine in refractory adult acute leukemia was conducted by the Southeastern Cancer Study Group from May 1979 to August 1980. Amsacrine, 90 mg/m2, was given daily for 5-8 days to 45 patients with acute myeloblastic leukemia, 15 patients with acute lymphoblastic leukemia, and six patients with blastic transformation of chronic granulocytic leukemia. Of the 66 patients entered in the study, 59 (89%) were evaluable for response. Complete remissions were observed in eight of 41 evaluable patients with acute myeloblastic leukemia (20%) and in three of 12 with acute lymphoblastic leukemia (25%). Remissions were short-lived (median, 7.9 weeks; range, 2-27). Toxic effects included the expected myelosuppression (100%), as well as moderate to severe stomatitis (46%), hyperbilirubinemia (30%), and supraventricular tachycardia (1.5%). This cooperative group pilot study confirms previous reports from single institutions that amsacrine is a useful drug in the treatment of refractory adult acute leukemia and is worthy of further study.
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PMID:Amsacrine in refractory adult acute leukemia: a pilot study of the Southeastern Cancer Study Group. 658 70

Aziridinylbenzoquinone is a quinone compound capable of penetrating the central nervous system. It has demonstrated activity against both intracranial and i.p. murine tumors and human tumor xenographs. We have conducted a Phase I trial of aziridinylbenzoquinone in 60 children with advanced cancer who were refractory to conventional therapy. The drug was given by slow i.v. push on a daily schedule for 5 days every 3 to 4 weeks. The dose range explored included 6 dose levels, ranging from 6 to 12 mg/sq m daily for 5 days in patients with solid tumors and leukemia, and in patients with leukemia, 20, 25, and 30 mg/sq m daily for 5 days. Myelosuppression was the dose-limiting side effect. In patients with solid tumor the highest dose studied was 12 mg/sq m, and the median nadir white blood cell and platelet counts were 0.7 X 10(3) and 6.0 X 10(3)/microliter on Days 17 and 22, respectively. The median recovery day for white blood cells was 39. There may be some evidence of cumulative toxicity with prolonged thrombocytopenia. Other side effects were mild nausea, vomiting, and mucositis. Elevations in liver enzymes and bilirubin were transient and dose dependent, occurring 3 to 4 weeks after drug administration. Of the 34 children with solid tumors, 33 were evaluable for hematopoietic toxicity, 3 were early deaths, and 31 receiving a total of 55 courses were evaluable for therapeutic response. Partial responses lasting 3 weeks to 6 months were seen in the 4 patients with Hodgkin's disease, and in a child with a metastatic spinal cord ependymoma. Fifty-two courses were given to 9 patients with acute lymphocytic leukemia and 17 with acute nonlymphoblastic leukemia. Of the 15 patients with acute nonlymphoblastic leukemia treated at doses greater than or equal to 25 mg/sq m/day for 5 days there was one early death and there were 2 M1 (less than or equal to 5% blasts with normal cellularity), 3 M2A (6 to 15% blasts), and 2 M2B (16 to 39% blasts) bone marrow responses lasting 1 to 3.5 months. Aziridinylbenzoquinone demonstrated activity against acute nonlymphocytic leukemia with maximal tolerated doses of 30 mg/sq m daily for 5 days. Its effect in Hodgkin's disease is encouraging; however, further study will be required to determine its efficacy in central nervous system cancers. Recommended doses for Phase II studies, using daily schedule for 5 days in children with solid tumors, is 9 mg/sq m, and in children with leukemia, it is 25 mg/sq m.
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PMID:Phase I study of aziridinylbenzoquinone (AZQ, NSC 182986) in children with cancer. 669 81

High-dose cytarabine (HDARA-C) at doses ranging from 1000 to 3000 mg/m2 administered as 30-min iv infusions was used in 12 patients with acute leukemia. HDARA-C toxicity was marked by nausea, vomiting, and somnolence; fever occurred in one patient. Myelosuppression was brief and reversible; the wbc count nadir occurred between Days 10 and 15 after treatment. In this study of a limited number of patients, no reliable conclusions could be drawn about antileukemic activity. However, (a) HDARA-C appeared to be a well-tolerated regimen in acute myeloblastic leukemia in complete remission; (b) a clear improvement was obtained in a patient with central nervous system leukemia; and (c) a sharp but transient decrease in peripheral blast cell counts was seen in two patients with acute myeloblastic leukemia. Cytarabine distribution was bi- or tri-compartmental; plasma final half-life was greater than 4 hrs in six patients. Pharmacokinetic parameters were not correlated with serum deoxycytidine deaminase activity. HDARA-C crosses the blood-brain barrier and may be useful in the prophylaxis against and treatment of central nervous system leukemia.
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PMID:High-dose cytarabine in acute leukemia: toxicity and pharmacokinetics. 685 Jun 54

Twenty-one patients with leukemia and lymphoma refractory to conventional therapy were treated with thymidine (dThd) at a dose of 75 g/m2/day for 48 h by continuous intravenous (IV) infusion, followed by cytosine arabinoside (ara-C) on an escalating dose schedule of 25-625 mg/m2/day for 48 h by continuous IV infusion. Toxicity included somnolence (1 patient), mucositis (2 patients), and myelosuppression (19 patients). One patient died prior to completion of therapy. Because of the patient population studied (mainly consisting of patients with leukemia refractory to conventional therapy) and the prevalence of myelosuppression prior to therapy, a median toxic dose was not evaluable. Therapeutic responses included a partial remission in a patient with acute myelogenous leukemia (AML) refractory to ara-C. An additional six patients with acute leukemia refractory to ara-C transiently cleared their peripheral blood of blasts, and a decrease in circulating blasts was noted in two other patients. Biochemical studies conducted on the peripheral blasts of two patients confirmed an enhancement by dThd of the incorporation of ara-C into the DNA of circulating blasts.
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PMID:A phase I-II study of combination therapy with thymidine and cytosine arabinoside. 688 25

Thirteen patients with relapsed acute leukemia, 12 adults with acute nonlymphocytic leukemia, and one child with acute lymphoblastic leukemia were treated with VP 16-213, an epipodophyllotoxin analog, at a dose of 200-300 mg/m2/day X5 as a 2-hour intravenous infusion. Only four patients achieved bone marrow aplasia and three regenerated with leukemic cells. The fourth patient achieved a partial remission for 4 weeks. Toxicities included myelosuppression (WBC nadir 500/microliter), nausea and vomiting (70% of courses), mucositis (23%), esophagitis (12%), which contributed to death in one patient, hypotension (12%), and transient liver function abnormalities (12%). It is concluded that increasing the dose of VP 16-213 as employed in this study did not increase the therapeutic activity of VP 16-213 for the treatment of relapsed leukemia but did increase the risk of toxicity.
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PMID:High-dose VP 16-213 (NSC 141540) for the treatment of patients with previously treated acute leukemia. 693 27

Seventy-six patients with advanced acute leukemia refractory to conventional chemotherapy were treated with a sequential combination of methotrexate (MTX) and L-asparaginase (L-ASP), based on the reported schedule-dependent synergism between the two drugs in human leukemic cells in vitro. On Day 1, patients received 60 mg/m2 of MTX iv, followed 24 hours later by L-ASP at a dose of 10,000 IU/m2 iv. This sequence was repeated weekly with 50% escalations in the dose of MTX with each course. Overall, 31 of 76 patients (40.7%) achieved complete remission after a median of three courses; the response rate was 35.5% in patients with acute nonlymphocytic leukemia (21 of 59 patients) and 58.8% in patients with acute lymphocytic leukemia (ten of 17). Increasing the starting dose of MTX to 200 mg/m2 did not improve the response rate. Maintenance therapy with the same combination given every 2 weeks produced a median complete remission of 10 weeks. Toxicity was manifested by: acute hypersensitivity reactions to L-ASP (five patients), stomatitis (36 patients), and mild liver abnormalities (five patients). MTX in doses up to 200 mg/m2 caused minimal myelosuppression. We conclude that the MTX-L-ASP combination is a well-tolerated, highly effective induction regimen for refractory acute leukemia.
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PMID:Sequential combination of methotrexate and L-asparaginase in the treatment of refractory acute leukemia. 693 51

AMSA was evaluated in the treatment of 109 adults with previously treated acute leukemia. Of the 102 evaluable patients, 82 had AML, 17 ALL, and 3 CML in blastic phase. A number of different dose schedules of AMSA were explored, and we conclude that the optimum dose of AMSA for remission induction in acute leukemia is 120 mg/sq m/day for 5 days. Complete remissions were observed in 23 (28%) patients with AML and in 1 patient with ALL. Patients who achieved complete remission were maintained on AMSA using a dose of 30-40 mg/sq m/day for 5 days repeated at 4-wk intervals. The median duration of complete remission was 12 wk (3-59 wk), and the responders survived significantly longer than the failures (27 wk versus 8 wk, p = 0.002). The side effects associated with AMSA therapy included mild nausea and vomiting, stomatitis, diarrhea, phlebitis, alopecia, and myelosuppression-related infections. Our results indicate that AMSA is a useful new antileukemic agent for the treatment of relapsed acute leukemia and appears to have activity comparable to that of the currently available drugs, such as cytarabine and the anthracycline antibiotics.
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PMID:Evaluation of AMSA in previously treated patients with acute leukemia: results of therapy in 109 adults. 695 87

The most effective schedule of cytosine arabinoside (Ara-C) administration remains controversial and is further confused by the use of combination chemotherapy. Two remission induction regimens comprising adriamycin, Ara-C, and 6-thioguanine have been compared in patients with acute myelogenous leukemia. Administration of Ara-C by continuous intravenous infusion resulted in faster clearing of leukemic blasts from the peripheral blood and bone marrow than after administration of the same dose by twice daily intravenous injection. Myelosuppression and gastrointestinal toxicity were, however, more pronounced when Ara-C was given by infusion. The complete remission rate was higher in the patients treated with intravenous infusions. It is too early to assess the duration of remission in the infusion study; however, despite the relatively low remission rate, 80% of patients under the age of 60 in the intravenous bolus study remain in remission with a minimum follow-up of two years.
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PMID:A comparison of two schedules of cytosine arabinoside used in combination with adriamycin and 6-thioguanine in the treatment of acute myelogenous leukemia. 696 18


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