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)

Thirty-five patients with acute myelogenous leukemia were treated with aclacinomycin A (60 mg/m2/day for 5 days) and VP-16-213 (100 mg/m2/day for 5 days). All were previously treated and had relapsed or were refractory to primary treatment. Most patients (28) had received prior DAT (daunorubicin, cytosine arabinoside, and 6-thioguanine) induction therapy followed by one or more courses of high-dose cytosine arabinoside (HD-Ara C) as consolidation therapy or as treatment for relapse. One patient was in her fourth relapse, one had relapsed acute megakaryoblastic leukemia (following remission with DAT and HD-Ara-C), one had a treatment-induced leukemia, and four patients were treated for primary treatment failures following two induction courses with DAT or a similar regimen. Fourteen patients had infections at start of therapy. Ten patients died within 14 days of treatment, all from sepsis or bleeding, before their marrow could be evaluated for leukemic response. Fourteen patients (40%) responded; 12 (34%) entered complete remission and two (6%) a partial remission (PR). Two of the four patients who were treated for primary treatment failures went into CR. The median CR duration was 99 days (range 30 to 455 days). Side effects from this treatment were similar to the conventional DAT regimen, although the gastrointestinal toxicity and mucositis appeared to be more severe. In addition, two of the patients had severe but reversible ventricular arrhythmias. The overall response (40%) and CR rate (34%) in this group of previously treated AML patients is encouraging, and further studies are needed to evaluate these preliminary findings.
 ...
PMID:Aclacinomycin A and etoposide (VP-16-213): an effective regimen in previously treated patients with refractory acute myelogenous leukemia. 316 95

From January 1985 to May 1987, we studied 256 adults with newly diagnosed acute leukemia. Acute undifferentiated leukemia (AUL) was diagnosed in 12 of the 256 (4.6%) cases when lineage could not be delineated by light microscopy and light cytochemistry. To further characterize the blasts, immunophenotyping, ultrastructural myeloperoxidase (UMPO), and ultrastructural platelet peroxidase parameters were examined in 10, 11, and 6 of the 12 cases, respectively. Five cases demonstrated UMPO and were reclassified as acute myeloblastic leukemia (AML). Of the six UMPO-negative cases, three had a myeloid and one had a mixed immunophenotype. One UMPO-negative patient with a myeloid immunophenotype was probed for the immunoglobulin heavy chain gene (JH) and the beta chain of the T-cell receptor gene (Tcr beta) with no evidence of rearrangement. Six cases were treated with standard acute lymphoblastic leukemia (ALL) chemotherapy and failed to achieve complete remission (CR). Various AML chemotherapeutic regimens produced CR in only 3 of the 12 cases. One case was treated with gamma interferon and the other 2 with high-dose Ara-C. Our findings indicate a myeloid lineage can be detected by UMPO (5/12) in some cases of AUL. A germline configuration with JH and Tcr beta in one case as well as a myeloid immunophenotype in 3 UMPO-negative cases raises the possibility that myeloid lineage commitment may occur in the absence of myeloid peroxidase (MPO) cytochemical positivity.
 ...
PMID:Heterogeneity in acute undifferentiated leukemia. 319 52

Human DNA ligase was purified from different kinds of immunocompetent cells: thymocytes, normal and stimulated lymphocytes, blasts from ALL (Burkitt and non-T, non-B) and ANLL (M1, M2, and M5). Based upon the protocol for the treatment of these leukemias, the purified enzymes were assayed in the presence of routinely used combinations of antileukemic drugs. At the range of concentration tested (between 0.1 and 5 microM) some drugs taken separately were totally inactive on the enzyme from the different sources. For those being inhibitory, when used in combination their effect was always different from what was observed when the compound was tested alone. Some combinations were more effective in inhibiting the enzyme from leukemic than from normal cells (vincristine + cyclophosphamide + prednisone in ALL and rubidazone + Ara-C, Ara-C + m-AMSA, in ANLL). However, some combinations of drugs are without effect on ligase from leukemic cells at this dose range (vincristine + rubidazone + Ara-C + prednisone and adriamycin + asparaginase + Ara-C in ALL or etoposide + Ara-C, adriamycin + cyclophosphamide in ANLL). This is the first direct observation of the effect of cytostatic drugs on DNA ligase, a key enzyme of the DNA replication and repair process. The clinical consequences of these observations are discussed in an attempt to selectively inhibit replication, thereby division, of cancer cells.
 ...
PMID:Effects of clinical combinations of antileukemic drugs on DNA ligase from human thymocytes and normal, stimulated, or leukemic lymphocytes. 325 60

Human recombinant GM-CSF (rGM-CSF) is under investigation as a growth-protective agent for normal hematopoietic elements in phase I trials of myelosuppressive chemotherapy and in bone marrow transplantation. We determined the effect of rGM-CSF on the metabolism of high dose Ara-C in bone marrow mononuclear cells (BMMCs) from healthy volunteers and patients with ANLL. Cells were incubated with rGM-CSF alone, Ara-C alone, or a combination of the two drugs. Treatment with rGM-CSF alone yielded approximately a twofold increment in intracellular dCTP pools in normal BMMCs but not in leukemic blasts. Exposure to rGM-CSF in conjunction with Ara-C corrected Ara-C-mediated declines in dCTP levels and decreased cytosine arabinoside triphosphate (Ara-CTP) accumulation in normal BMMCs but not in their leukemic counterparts. Furthermore, when exposure to Ara-C was preceded by treatment with rGM-CSF for 18 hr, an even greater reduction in the Ara-CTP/dCTP pool ratio was observed in normal versus leukemic elements; however, this did not significantly change Ara-C DNA incorporation in the two cell types. The differential effect of rGM-CSF on the phosphorylation of Ara-C in normal BMMCs versus leukemic blasts has potential implications for the use of a regimen consisting of rGM-CSF and high dose Ara-C in the treatment of ANLL with chemotherapy or autologous bone marrow transplantation.
 ...
PMID:Effect of recombinant GM-CSF on the metabolism of cytosine arabinoside in normal and leukemic human bone marrow cells. 326 63

High doses of cytosine arabinoside (ara-C) were administered by continuous infusion to 24 patients with acute leukemia in relapse or blast phase of chronic myelogenous leukemia (CML). Ara-C was infused at a dose rate of 250 mg/M2/hr for 36 to 72 hr. The major toxicities were myelosuppression, diarrhea, and abdominal pain. Other toxicities included pulmonary edema, neurotoxicity, and liver function abnormalities. The gastrointestinal toxicity was dose-limiting and a phase II dose was established at 250 mg/M2/hr for 60-72 hr. Four patients treated with this dose schedule had objective responses. Two patients with CML in blast phase returned to chronic phase and have remained stable without maintenance therapy for 12 and 18 months. Two patients with acute myelogenous leukemia in relapse entered complete remissions which continued unmaintained for 4 and 6 months. Steady-state plasma ara-C levels ranged between 7 and 24 x 10(-6) M, while ara-U levels were as high as 4.5 x 10(-4) M. There was no detectable accumulation of ara-C or ara-U during the infusion period. These findings would suggest that the continuous infusion of high dose ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.
 ...
PMID:Prolonged high dose ARA-C infusions in acute leukemia. 328 17

Both harringtonine (Harr) and Ara-C are effective for treatment of ANLL. Since it was suggested that Harr could induce leukemic cells to differentiate and Ara-C might be a weak inducer of leukemic cell differentiation, we investigated the effect of Harr in combination with Ara-C on inducing differentiation of leukemic cells. Ten patients with ANLL were treated with low dose Harr in combination with low dose Ara-C. Complete remission was achieved in 8 of the 10 patients. After therapy, severe pancytopenia and moderate myelosuppression occurred in two patients who achieved remission. Four patients demonstrated a decrease in blast cells with an associated transient increase in mature granulocytes during therapy. Auer bodies appeared in 7-8% mature granulocytes in peripheral blood and in bone marrow on the 14th day of combination therapy in one patient. Freshly isolated leukemic cells from six pretreatment patients were cultured in liquid in the presence of Harr in combination with Ara-C. Apparent evidence of differentiation of leukemic cells and Auer bodies in the cytoplasm of mature granulocytic cells were observed in two of the six patients. The above results seem to suggest that the therapeutic effect of low dose Harr plus low dose Ara-C may result from both differentiation induction and cytotoxicity of the leukemic cells.
 ...
PMID:A study on the induction of differentiation of human leukemic cells by harringtonine combined with cytarabine. 341 24

The effect of retinoic acid (RA) alone and in combination with cytosine arabinoside (Ara-C) on differentiation of fresh human myeloid leukaemic cells from patients with AML was studied. Cells from six patients: three with acute myelomonocytic leukaemia AMMoL and three with acute monoblastic leukaemia AMoL with a percentage of blasts greater than 70, were treated in an in vitro primary suspension culture with retinoic acid (10(-7) M), cytosine arabinoside (100 ng/ml) or both in combination. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in RPMI 1640 culture medium supplemented with 20 per cent fetal bovine serum and 10 per cent (PHA-LCM) phytohaemagglutinin leucocyte conditioned medium and incubated for 6 days at 37 degrees C in a humidified incubator containing 5 per cent CO2 in air. Morphological and functional differentiation into terminal mature elements was induced in all leukaemia cells of the six patients following exposure to the combination of both agents. These results suggest the potential usefulness of the combination of a differentiating agent (retinoic acid) and an antileukaemic drug (cytosine arabinoside) in the treatment of acute myeloid leukaemias: AMMoL and AMoL. This combination warrants a clinical trial.
 ...
PMID:Retinoic acid alone and in combination with cytosine arabinoside induces differentiation of human myelomonocytic and monoblastic leukaemic cells. 342 32

A 57-year-old-male patient with acute myelogenous leukemia in second relapse who was refractory to BHAC . AMP [behenoyl arabinosyl cytosine (BHAC), aclacinomycin, 6-mercaptopurine and prednisolone (PSL)] and BHAC . DVP [BHAC, daunomycin, vincristine and PSL] was treated with an intermediate-dose cytosine arabinoside (ID Ara-C) regimen. This schedule consisted of a 1-h infusion of Ara-C at a dose of 500 mg/m2 every 12 h for 6 d (days 3-8), in combination with doxorubicin 50 mg/m2 on day 1 and vincristine 1 mg/m2 on day 2. The patient achieved a complete remission 23 days after completion of Ara-C and was treated with ID Ara-C (Ara-C days 3-6) as a consolidation. Remission duration was only 2.5 months. Plasma Ara-C concentrations were assayed by HPLC and the peak level was 6.7 micrograms/ml. Side effects were mild nausea, vomiting, alopecia and moderate skin rash.
 ...
PMID:[A case of complete remission from acute myelogenous leukemia in second relapse achieved using an intermediate-dose cytosine arabinoside (ID Ara-C) regimen]. 345 5

Two childhood acute myelogenous leukemia (AML) patients receiving intrathecal (IT) and intravenous (IV) cytosine arabinoside (Ara-C) developed progressive ascending paralysis, resulting in death in one patient. Necropsy findings on this patient included spinal cord demyelination characteristic of Ara-C neurotoxicity. An unusual aspect of these two cases was the delay between cessation of IT therapy and the onset of neurologic symptoms. These patients received relatively low total doses of IT Ara-C and standard doses of IV Ara-C. Previous studies have shown that Ara-C equilibrates readily between serum and cerebrospinal fluid; this implies that total IV and IT doses of Ara-C may be additive in relation to development of neurotoxicity. For these reasons, use of IV and IT Ara-C in childhood AML must be approached with greater caution, especially if neurologic abnormalities develop during or after therapy.
 ...
PMID:Progressive ascending paralysis following administration of intrathecal and intravenous cytosine arabinoside. A Pediatric Oncology Group study. 345 42

This study was designed to evaluate the effect of low-dose Ara-C in the treatment of refractory, atypical leukemia and myelodysplastic syndrome (MDS). The subjects were 33 patients (19 acute myelocytic leukemia (AML), 9 MDS, 3 atypical leukemia and 2 unclassified leukemia). The age range was 19 to 84 years with a mean age of 51.5 years. We administered low-dose Ara-C (5-10 mg/m2/12 h s.c. or i.v.) for 13 to 35 days with a mean of 16.7 days. Complete remission and partial remission were obtained in 8 of 31 (25.8%) and in 9 of 31 (29.0%) respectively. A high response rate was found in M2 types showing a tendency for mature and refractory anemia with excess blasts in MDS according to the FAB classification. In our cases, severe pancytopenia in peripheral blood as a result of Ara-C was observed before normal hematopoiesis recurred. From the above results, the mechanism of low-dose Ara-C may induce remission by a cytotoxic rather than a differentiation effect. This treatment can be offered to patients with refractory, atypical leukemia and MDS with limited toxicity.
 ...
PMID:[Effect of low-dose Ara-C in the treatment of refractory, atypical leukemia and myelodysplastic syndrome]. 345 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>