UMLS:C0023418 - FACTA Search

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Query: UMLS:C0023418 (leukemia)
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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

6-Mercaptopurine (MP)-sensitive and -resistant cell culture lines were used to further characterize the apparent ability of MP nucleotide derivatives to overcome resistance to the parent drug. 6-Mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [MPRP], bis(6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(MPR)P], bis(O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(dibut.MPR)P], and O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [dibut.MPRP] were tested for cytotoxic and/or growth inhibitory effects against MP-resistant sublines of V79 Chinese hamster lung fibroblasts (CH/TG) and L1210 mouse leukaemia cells (L1210/MPR) in which deficiencies of hypoxanthine-guanine phosphoribosyltransferase, and hence drug nucleotide forming capacity were the basis of resistance. L1210/MPR cells were totally resistant to 1 mM 6-mercaptopurine-9-beta-D-ribofuranoside [MPR] and 2 mM MPRP, but were inhibited by high concentrations (greater than 0.25 mM) of bis(MPR)P. These results suggested that bis(MPR)P was taken up by cells as the intact molecule since MPR and MPRP were its extracellular breakdown products. L1210/MPR cells were much more sensitive to the lipophilic bis(dibut.MPR)P derivative which had a predominantly cytotoxic action as judged by trypan blue staining and the ability of treated cells to produce macroscopic colonies in soft agar medium. However, cells killed by bis(dibut.MPR)P did not disintegrate appreciably over periods of up to 10 days. The effects of bis(dibut.MPR)P were probably the result of cellular uptake of the intact molecule. Dibut.MPRP showed minimal ability to inhibit L1210/MPR cells although this compound was a possible breakdown product of bis(dibut.MPR)P and a source of the same extracellular degradation products. The median cell size decreased in L1210/MPR cultures during exposure to both bis(MPR)P and bis(dibut.MPR)P. This effect was elicited more rapidly and at lower concentration by bis(dibut.MPR)P than by bis(MPR)P. In contrast, sodium butyrate, a breakdown product of bis(dibut.MPR)P induced increases in cell size at high concentration. Bis (dibut.MPR)P was also cytotoxic to MP-resistant CH/TG cells and was approximately 300 times more effective than bis(MRP)P and MPR which exhibited similar activity against this cell line. Bis(dibut.MPR)P and dibut.MPRP were equivalent and less active than MPR in their effects on MP-sensitive L1210/0 cells where their predominant mechanism of action was via degradation to release MPR.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effects of 6-mercaptopurine nucleotide derivatives on the growth and survival of 6-mercaptopurine-sensitive and -resistant cell culture lines. 383 80

Combination chemotherapy using the water-soluble nitrosourea MCNU with various anti-cancer agents was studied using L1210 leukemia and P388 leukemia. In titration experiments MCNU showed remarkable antitumor effects at doses from 5 mg/kg to 80 mg/kg, producing numbers of 60-day survivors with L1210 leukemia. In L1210 leukemia, respective combinations of MCNU with the antimetabolites, MTX, 6-MP, 6-TG, MCNU, 5-FU and Cyclo-C showed enhanced antitumor effects. MCNU combined with each of ADR, MMC and CPM also showed marked anti-tumor effects with 60-day survivors. In P388 leukemia MCNU combined with each of ADR, MMC, VDS and CPM produced strong anti-tumor effects with numbers of 60-day survivors. In the results of these combinations, especially the combinations of MCNU + 5-FU in L1210 leukemia and MCNU + CPM in both L1210 and P388 leukemia, a significant increase in mean survival time was achieved. These combinations also produced many 60-day survivors which were considered to be due to the synergistic antitumor effects of the combined drugs.
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PMID:[Effects of combination chemotherapy of MCNU with various anti-cancer agents]. 391 6

Ethyl-O-[N-(p-carboxyphenyl) carbamoyl]-mycophenolate (CAM), a mycophenolic acid (MPA) derivative, has been evaluated in terms of influence of treatment schedule and route of administration on antitumor activity in mice bearing L 1210 leukemia and cross-resistance to 6-MP was studied. The results obtained were as follows; The effect of oral administration of CAM was identical to that of MPA or FT-207. Both CAM and MPA were most effective when given on day 1, 5 and 9 following tumor inoculation. Intraperitoneal administration with MPA was marginally effective, while the activity obtained with intraperitoneal administration of CAM was superior to that for oral administration. CAM did not show any cross-resistance to 6-MP.
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PMID:[Effect of ethyl-O-[N-(p-carboxyphenyl) carbamoyl]-mycophenolate against L1210 leukemia]. 407 27

6-Mercaptopurine is extensively used in the treatment of childhood lymphoblastic leukaemia to prolong the duration of remission achieved with other drugs. The response to remission maintenance therapy varies widely. We investigated the relationship between red blood cell 6-thioguanine nucleotide, a metabolite of 6-mercaptopurine, and myelosuppression in 22 children with acute lymphoblastic leukaemia in remission. The peripheral neutrophil count was used as an index of myelosuppression. 6-Mercaptopurine dose was related to 6-thioguanine nucleotide concentration (r = 0.4; P less than 0.001; n = 90; y = 18.51 + 0.36 x). Large individual variations around the regression line are observed. Neither 6-mercaptopurine dose nor 6-thioguanine nucleotide concentration was related to the neutrophil count at the time of sampling (day 0) or 7 days later. Both 6-mercaptopurine dose and 6-thioguanine nucleotide concentration correlated with the neutrophil count at day 14 (r = -0.33; P less than 0.01; n = 90 and r = -0.3; P less than 0.01; n = 90 respectively). This delay is compatible with a cytotoxic action on bone marrow stem cells. Excluding children with other, uncontrolled, potentially myelosuppressive influences the correlation between 6-thioguanine nucleotide concentration and neutropenia improved (r = -0.6; P less than 0.001; n = 37). A significant degree of neutropenia was observed by day 14 if the 6-thioguanine nucleotide concentration (day 0) was greater than 210 pmol/8 X 10(8) RBCs. The assay of 6-thioguanine nucleotide may highlight those individuals with pharmacokinetic resistance. Two children on continuous high dose 6-mercaptopurine, had low red blood cell 6-thioguanine nucleotide concentrations and neutropenia was not observed.
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PMID:Childhood leukaemia: a relationship between intracellular 6-mercaptopurine metabolites and neutropenia. 657 34

58 children were admitted to a prospective randomized leukemia induction and CNS-prophylaxis three different protocols were followed for maintenance. A (n = 20): 6-MP (50 mg/m2) p.o. daily + MTX (20-30 mg/m2) p.o. weekly; B (n = 20): 6-MP (50 mg/m2) p.o. daily + MTX (75-150 mg/m2) i.v. every two weeks; C (n = 18): 6-MP (50 mg/m2) p.o. daily + alternating 8-week-courses of four biweekly i.v. injections of MTX (75-150 mg/m2) and four biweekly i.v. injections of Cyclo (600 mg/m2). After all patients have been followed for at least 48 months, the rates of continuous complete remission are 42% in protocol A, 63% in protocol B, and 29% in protocol C. No encephalopathies have been observed with regimen B.
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PMID:[Which is the best methotrexate schedule for maintenance therapy of childhood ALL? A randomized study]. 675 58

Thirty eight patients with acute lymphoblastic leukemia were treated protocol 0171 (VCR, PRED, MTX, cyclophosphamide +/- +/- 6-MP) and protocol 0276/A (VRC, PRED, L-ASP, MTX, 6-MP, cyclophosphamide). Overall complete remission rate in both studies was 84--85%, and additional treatment in protocol 0171 resulted in complete remission rate of 92%. Median duration of complete remission in protocol 0171 was 23 months and median survival of all patients was 33 months. Six patients randomized to regimen "A" (without 6-MP in intensification) had median duration of complete remission 8 months and media survival was 13 months. Seventeen patients treated with regimen "B" (with 6-MP in intensification) had median duration of complete remission 25 months and median survival was 39 months. Median survival of patients allocated on protocol 0276/A in 21+ months and median duration of complete remission is 23 months at present. Twelve percent of patients treated with the best regimen have survived more than 66 months in continuous complete remission. The incidence of drug related death in complete responders was 6%. The relapses were most frequent during the first two years of remission. Extramedullary leukemia as the initial site of relapse was observed in 9% of patients.
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PMID:Treatment of adult acute lymphoblastic leukemia: results of two trials. 702 59

Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium excretion can be reduced by diuretics or fluoxetine. When drugs such as antifungal imidazoles, azapropazone, or phenylbutazone are permitted to inhibit the metabolism of sulphonylureas, hypoglycemic effects are enhanced and, if unnoticed, may cause brain damage. Fibrates should not be combined with HMG-CoA reductase inhibitors because of the increased risk of myopathy. Patients taking non-selective monoamine oxidase inhibitors should avoid amine-containing foods and drugs such as matured cheeses, meat, yeast extracts, some wines, unfresh protein, and cold-curing medications. The metabolism of azathioprine is inhibited by allopurinol, and this combination requires a reduced dosage of azathioprine. Mercaptopurine, used in the treatment of leukemia, is also a metabolite of azathioprine. Sources of comprehensive information on drug interactions are 1) the "British National Formulary," appendix 1; 2) Chapter 10 of "The Oxford Textbook of Clinical Pharmacology and Drug Therapy"; and 3) a monograph by Stockley entitled "Drug Interactions."
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PMID:Serious drug interactions. 790 48

Sixty patients consisting of 56 cases with leukemia, 3 with lymphoma and 1 with neuroblastoma were treated with various kinds of hematopoietic stem cell transplantation. The conditioning regimen consisted of mainly cyclophosphamide (CTX) and total body irradiation (TBI) with the addition of 1-3 doses of other antitumor drugs e.g. cytarabine, daunomycin, etoposide, 6-MP etc. The overall incidence of hemorrhagic cystitis in the course of transplantation was 23.3% (14 out of 60 patients). The time of onset of hematuria in 6 of 14 patients was within 1-4 days following high-dose CTX during conditioning and in the remaining 8 cases occurred 10-30 days after transplantation. The duration of hematuria lasted 2-31 days (mean, 4 days). Thirteen patients recovered and one patient died from the complication.
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PMID:[Hemorrhagic cystitis in the course of hematopoietic stem cell transplantation]. 790 67

The modern treatment of acute myelogenous leukemia (AML), consists of a polychemotherapeutic induction treatment followed by a post-remission therapy of variable intensity and duration and acute promyelocytic leukemia (APL) does not differ from this behavior. However, differently from the other AML subtypes, APL shows a high response rate to induction monochemotherapies with anthracycline drugs. This high response rate to anthracycline monochemotherapies is very peculiar of APL. Moreover, it has been suggested that maintenance treatment regimens incorporating the drugs Methotrexate and 6-Mercaptopurine, two drugs generally not utilized in the post-remission treatment of other AML subtypes, may be effective in prolonging the leukemia-free survival of APL. Furthermore, the results firstly obtained by a Chinese group in 1988 by using the vitamin A derivative all-trans retinoic acid (ATRA) have been successively confirmed by several other groups in the world. Therefore, at present the all-trans retinoic acid appears to be the best CR inducer in APL. However, these CRs are short lasting when maintained with ATRA alone and eventually all patients relapse. As a consequence, patients achieving CR with ATRA still require intensive post-remission chemotherapy to maintain the CR. As for bone marrow transplantation procedures, it is our opinion that they do not represent the treatment of choice of APL in first CR considering the very good results obtained with standard pharmacological approaches. In conclusion, only future randomized prospective trials will clarify which, among the several proposed therapeutic approaches, should be preferred in this very peculiar subtype of AML.
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PMID:What is the best treatment for acute promyelocytic leukemia? 812 30

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