Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From 1987 to 1990, intensive postremission chemotherapy was compared to autologous bone marrow transplant in previously untreated children with AML who received identical induction therapy with two courses of Daunorubicin (DNR) and conventional dose ARA-C (protocol AIEOP LAM 87). Overall, 121 of the 155 eligible patients achieved complete remission (CR) (78%). Patients in CR who lacked HLA-MLC compatible donor were randomized to receive either autologous BMT (Auto-BMT) or further sequential postremission therapy. Patients with HLA-MLC compatible donor were assigned to allogeneic BMT (Allo-BMT). Projected 3-years disease free survival (DFS) are 58% for Allo-BMT group, 24% for Auto-BMT group, 26% for chemotherapy group and 30% for a group of not randomized patients (intention to treat analysis). On March 1990 a pilot study LAM 87M was initiated. Patients in CR after induction therapy (identical to the previous protocol) receive a single intensification course consisting of high dose ARA-C plus DNR. The study continues to accrue patients.
Leukemia 1992
PMID:Therapeutic strategies for postremission treatment in childhood acute myeloid leukemia (AML). The AIEOP experience 1987-1991. 157 40

The results of four consecutive trials designed by the GIMEMA group for the treatment of ANLL in elderly patients are reviewed. Complete remission (CR) has been achieved in 20.8% of patients older than 60 years treated with 5-day courses of ARA-C plus thioguanine, in 22.7% of patients treated with high dose ARA-C (HDARAC) plus Asparaginase, in 39.5% of patients aged 55 to 80 receiving either Idarubicin or Daunorubicin in combination with Cytarabine in a standard 3+7 protocol and in 51% of patients older than 60 years treated with intermediate dose ARA-A (IDARAC) plus Mitoxantrone. From 1988, patients ineligible for aggressive chemotherapy entered a study of palliative treatment with Thioguanine and ARA-C. This 18 year GIMEMA experience showed that: CR can be obtained only with regimens producing marrow aplasia, the inclusion of anthracyclines or Mitoxantrone improves the CR rate, without prohibitive toxicity, haematological toxicity is very high in elderly patients and account for the most frequent cause of treatment failure namely death in aplasia, palliative treatment does not improve the quality of life and prolongs median survival only slightly. When comparing the results of these trials, it appears that in the GIMEMA group the capability of offering effective treatment to elderly patients with ANLL has continuously improved and that IDARAC plus Mitoxantrone is so far the most active and best tolerated regimen. Death in aplasia remains a major problem and future trials will be aimed at exploiting the possibility of reducing the haematological toxicity by using recombinant colony stimulating factors.
Leukemia 1992
PMID:Treatment of acute non lymphoid leukemia (ANLL) in elderly patients. The GIMEMA experience. 157 48

Cancer and Leukemia Group B undertook a randomized trial of intensification treatment in adults aged 15 to 79 years with acute lymphocytic leukemia (ALL) in complete remission (CR). Daunorubicin (DNR), prednisone, vincristine (VCR), intrathecal (IT) methotrexate (MTX), and asparaginase produced 177 CRs in 277 patients. One hundred fifty-one patients were randomly assigned to receive treatment as follows: 74 received intensive cytarabine and DNR, and 77 received cycles of mercaptopurine (6-MP) and MTX, followed by 6MP, MTX, VCR, and prednisone for 3 years in all. One hundred twelve patients received CNS prophylaxis. Intensification produced major myelosuppression but did not improve remission duration (median, 21 months). Of the 151 patients with CRs who entered the intensification phase, 29% remain in continuous CR (43 to 117 months); in 19 patients, CRs have lasted for longer than 7 years. No relapses occurred after 60 months. Median survival from the time of randomization was 30 months. Those under 30 years of age responded more frequently, with longer CR and survival. While 53% of those aged 15 to 19 years remain in continuous CR, 92% of patients over 59 years have relapsed. The presence of a myeloid antigen on the leukemic cells was adversely prognostic for CR achievement and for survival. Pretreatment WBC and platelet levels independently affected CR duration and survival. Early M1 marrow development presaged longer remissions. CNS relapse occurred in 47 of 256 patients with normal CSF before treatment, in 29 before CNS prophylaxis. CNS disease occurred after CNS prophylaxis in 18 patients: 13 of 61 who had received standard premaintenance and five of 51 who received intensification. No advantage in CR duration or survival resulted from intensive treatment with DNR and cytarabine following induction of CR.
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PMID:The effects of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphocytic leukemia: a prospective randomized clinical trial by Cancer and Leukemia Group B. 194 Oct 59

During the 1970s, despite apparently similar treatment, the prognosis for children with lymphoblastic leukaemia (ALL) improved more in some countries, notably the United States and West Germany, than in others. To find out why, the first phase of the United Kingdom (UK) Medical Research Council (MRC) childhood ALL trial, UKALL VIII, was designed to see whether similar results to the United States Children's Cancer Study Group (CCSG) could be obtained in the U.K. using an identical protocol (CCG 162). Protocol 162 was one of a series of regimens devised by the American Children's Cancer Study Group in the 1970s and was used specifically for their average risk patients (all children with ALL with an initial white cell count up to 50 x 10(9)/l except those aged 3-6 years with white cell counts under 10 x 10(9)/l). One arm (1A) of their study was adopted by the MRC for all children in the U.K. aged 0-14 years with confirmed ALL. Eight hundred and twenty-nine consecutive patients were entered between 1980 and 1984. The first 199 patients formed a single arm study as per the original protocol 162 (arm 1A), but the subsequent 630 children were randomized to receive or not two doses of daunorubicin on the first 2 d of induction. This randomization was an attempt to answer the important question as to whether event-free survival was influenced by the use of four rather than three induction agents. A second randomization between 2 and 3 years continuing therapy was also introduced at this stage as it had been by the CCSG in their protocol. With a minimum follow up period of more than 5 years, disease-free survival for the whole group is 55%, a considerable improvement on all previous UKALL trials. Results for patients directly comparable with those in CCSG 162 ('average risk' patients) and their American counterparts were similar. Daunorubicin was associated with more early deaths but improved disease-free survival for those achieving remission. More children relapsed who stopped treatment after 2 years than those who continued for 3, but this was balanced by increased treatment mortality in the third year. The fact that for UKALL VIII the results were similar to those of the CCSG suggests that previous MRC protocols were not sufficiently sustained and intensive, particularly during the maintenance phase of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood). 206 56

Clinicopathological and cytogenetic features of two patients with acute myelogenous leukemia (AML) whose blast cells coexpressed myeloid-associated antigens and CALLA are described. Leukemia cells revealed myelomonocytic (FAB-M4) and monocytic (FAB-M5) features, while the nonblast cell population exhibited trilineage myelodysplasia in both cases, a finding suggestive of multiple-cell-lineage involvement. Cytogenetically, a deletion of the long arm of chromosome 6 was found in one patient, and normal metaphases were detected in the other. Molecular studies disclosed a rearrangement of the IgH locus in one patient. Clinically, these patients were unresponsive to antimyeloid regimens including Daunorubicin and Cytarabine, two agents normally also effective on lymphoblastic leukemias, possibly indicating the need for alternative protocols for the treatment of CALLA positive AML.
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PMID:Immunophenotypic, cytogenetic and molecular investigations in two cases of CALLA positive acute myeloid leukemia. 209 59

A case of two repeated CNS recurrences of acute non-lymphocytic leukemia (M2) was treated with intermediate dose Ara-C therapy and achieved 2 complete remissions. The clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in this patient were discussed. A 55-year-old male with acute non-lymphocytic leukemia (M2) achieved complete remission by combination chemotherapy of Behenoyl-ara-C, Daunorubicin, 6-Mercaptopurine and Prednisolone in July, 1985. He subsequently received consolidation and intensification therapy with periodical intrathecal injection of Methotrexate (MTX), but 13 months later he developed his first CNS recurrence which was resistant to the intrathecal administration of Ara-C and MTX. As he also relapsed systemically, Ara-C was administered in intermediate dose (1 g/m2 every 12 hrs for 5 days) and he achieved complete remission both in the CNS and systemic manifestations. Six months later he was diagnosed as having a second CNS recurrence and another systemic relapse. Intermediate dose Ara-C was administered again, and he achieved complete remission in the CNS and partial remission in systemic manifestations. Pharmacokinetic study revealed high peaks of Ara-C concentration in plasma (6.2 microM immediately after the end of the infusion) and high degree of its penetration into the CNS (5.6 microM at 3 hr after the end of the infusion) suggesting the effective and perhaps a uniform level of Ara-C is achieved throughout the CNS by this therapy. In 3 other patients without CNS involvement 0.88 +/- 0.44 microM of Ara-C, which is enough concentrations for its cytostatic effect, was detected at 3 hr after the end of infusion, suggesting the efficacy of the therapy for CNS prophylaxis. In this case the relapse occurred after repeated administration of antileukemic drugs, including Behenoyl-ara-C, an analog of Ara-C, and was resistant to the intrathecal administration of Ara-C. These findings suggest that intermediate dose Ara-C therapy was effective to overcome a resistance to antileukemic drugs, including Ara-C, and also, in some cases, more effective than intrathecal injection of antileukemic drugs for the treatment of CNS leukemia.
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PMID:[Clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in a patient with acute non-lymphocytic leukemia with two CNS recurrences]. 232 84

91 patients with acute nonlymphoblastic leukemia (ANLL) were treated with Homoharringtonine, Cytosine arabinnoside, Thioguanine (HAT) and/or Daunorubicin, (Adriamycin) Cytosine arabinnoside, Thioguanine D(A) AT protocols. The total CR rate was 68.1% with a median remission duration of 20.3 months, and the expectant survival rate in 5 years (Kaplan-Meier method) was 39%. The CR rate and the CR duration projected by HAT and D (A) AT protocols were very similar. After 20 prognostic factors from both clinical and laboratory examinations prior to treatment had been analysed, we concluded that (1) The CR rate was improved by increasing the dose of induction chemotherapy; (2) The patients might have longer remission and survival if they obtained remission in 2 courses of treatment; (3) The remission durations were comparable between the individuals receiving and not receiving maintenance chemotherapy.
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PMID:[Analysis of the therapeutic efficacy and prognostic factors of intensive chemotherapy in 91 patients with acute nonlymphoblastic leukemia]. 240 Nov 66

The pharmacokinetics of daunorubicin and doxorubicin were studied in plasma and leukemic cells from 16 patients with acute nonlymphoblastic leukemia during 19 courses of treatment with the unconjugated or DNA-conjugated drugs. Daunorubicin and doxorubicin are high-clearance drugs with very high apparent volumes of distribution, indicating a pronounced tissue affinity. This was more pronounced in the case of doxorubicin and may explain the reduced cardiotoxicity of the DNA-complexes. Daunorubicin reached higher intracellular peak concentrations than doxorubicin, but the latter drug was retained much longer. The cell/plasma concentration ratio was higher for daunorubicin than for its reduced metabolite daunorubicinol. No doxorubicinol was found intracellularly. The observed differences in cellular pharmacokinetics between daunorubicin and doxorubicin may explain the difference between the clinical activity spectras of these two drugs. DNA-conjugation did not markedly modify the uptake of daunorubicin in the leukemic cells, whereas the mean intracellular accumulation of doxorubicin was 60% higher when the drug was administered as a DNA-conjugate. This may enhance the selectivity of doxorubicin in the treatment of acute leukemia.
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PMID:Pharmacokinetics of daunorubicin and doxorubicin in plasma and leukemic cells from patients with acute nonlymphoblastic leukemia. 271 19

The human leukemia cell line K562 expresses constitutively high levels of c-myc mRNA and can be induced to differentiate along the erythroid lineage. Treatment of K562 cells with the antineoplastic drugs 1-beta-D-arabinofuranosylcytosine and daunomycin causes differentiation into hemoglobin-producing cells. The differentiation process is associated with an early block of cellular proliferation occurring during the first 24 h of treatment. RNA synthesis is progressively reduced to 20 to 30% of the control levels after 3 days of exposure to the drugs. Dot and Northern blot analyses were performed to evaluate the levels of c-myc or globin mRNA during the differentiation of K562. Daunomycin and 1-beta-D-arabinofuranosylcytosine, despite their distinct chemical nature, induced similar modulation of mRNA levels. Globin mRNA did not change during the first 24 h of culture and began to increase after 48 h of treatment with drugs, reflecting the kinetic of appearance of hemoglobin-producing cells. In contrast, a transient decrease of c-myc mRNA was observed after the first 24 h of drug treatment, followed by a return to normal levels of c-myc mRNA after 48 h of treatment. Thus, the expression of c-myc mRNA in K562 did not reflect their proliferative activity nor their stage of differentiation. We speculate that the transient down-regulation of c-myc mRNA may be an initial event in the erythroid differentiation of K562.
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PMID:Erythroid differentiation and modulation of c-myc expression induced by antineoplastic drugs in the human leukemic cell line K562. 347 95

A 47-year-old man, who had been diagnosed as having acute myelomonocytic leukemia (AMMOL) and had been treated with combination chemotherapy, was admitted to our hospital because he had developed melena. He had been judged to be in complete remission and had shown no signs of recurrence for years, Daunorubicin, vincristine 6-Mercaptopurine and Cyclophosphamide had been administered for maintenance and intensification therapy. He was well until January 1986, when this melena began. A barium enema was given and he was diagnosed as having rectal cancer. Amputation of the rectum and a permanent abdominal colostomy was made safely, mainly because he had been in complete remission, and he recovered normally after the operation. In recent years, the survival of patients with malignancies has improved due to aggressive treatment even in cases of hematological neoplasms. However, the risk of secondary neoplasms in patients treated for cancer has increased. This case suggests that we have to be careful when prescribing treatment for cancer patients, since anti-tumor drugs may have cartinogenic effects.
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PMID:[A case of successful surgical treatment of rectal cancer complicated by acute myelomonocytic leukemia]. 348 Sep 60


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