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)

Three patients with acute myeloblastic leukaemia and blast cell counts greater than 100 X 10(9)/1 (100 000/mm3) died unexpectedly soon after blood transfusion. In two cases postmortem examination disclosed cerebral leukostasis. Analysis of the records from the MRC's fourth and fifth acute myeloid leukaemia trials showed that in the first week after diagnosis mortality was five times greater in patients with blast counts above 100 X 10(9)/1 than in patients with lower counts. Age and platelet count did not explain this excess. The mean haemoglobin concentration in the patients with high blast counts who died within the first week was 10.5 +/- 2.8 g/dl, which was significantly higher than that in the surviving group (7.6 +/- 2.4 g/dl). Only half the patients received chemotherapy within two days of diagnosis. Leukostasis is an important cause of early death in patients with high blast counts, and the increase in viscosity produced by transfusing to a haemoglobin concentration above 10 g/dl may lead to sudden deterioration. Transfusion to such concentrations should be avoided until the blast count has been reduced by early chemotherapy.
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PMID:Leukostasis associated with blood transfusion in acute myeloid leukaemia. 27 61

Ten patients with ALL and 35 with AML received combination chemotherapy at out Institute during the period 1972 - 1975. Patients with ALL were treated according to the L-2 protocol, those with AML according to the L-2, MRC 5/A, MRC 5/B and TRAP protocols. Nine of the 10 patients with ALL entered complete remission, and median survival time of these patients was 9.2 months. Four of the 35 patients with AML achieved complete, 13 partial remission. Median survival in this group was 4 months. Infection and bleeding represented the most frequent and severe forms of complication. Bleeding was well controlled by the administration of platelet concentrates, but infections were often lethal. The poor results were probably due to the high incidence of severe infections.
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PMID:Combination chemotherapy in adults with acute leukaemia. 107 Apr 69

A link was proposed between human non-Hodgkin's lymphoma and exposure to 2,4,5-trichlorophenoxyacetic acid (245T) and pentachlorophenol (PCP). To test this view and the hypothesis that immune suppression or stimulation could affect B-cell lymphoma (BCL) induction, we administered chronically to MRC-Wistar (MRC-W) rats of both sexes 98% pure 245T (600 mg/kg diet), 86% pure PCP (500 mg/kg diet), methylprednisolone (20 mg/kg ip weekly), and Freund's adjuvant (0.5 ml im every 3-6 wk) for 40 wk, together with 75 mg 2-hydroxyethylnitrosourea (HENU)/l drinking water, a system known to induce B-cell lymphoma. The 245T was shown to contain only 1-4 micrograms/kg each of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF), but the PCP contained 25 micrograms TCDD and 670 micrograms TCDF/kg. HENU given alone induced B-cell lymphoma and osteosarcoma as before, with higher incidences of both tumors in males than in females. The B-cell lymphoma diagnosis was confirmed by immunologic typing of cell-surface markers and by probes for gene rearrangements. Coadministration with HENU of three of the four test agents did not affect tumor incidence, but PCP acted synergistically with HENU to induce acute myelocytic leukemia. PCP given alone or with HENU induced a 40-67% incidence of liver cell adenomas in the female rats. These effects were probably not due to TCDD in the PCP. HENU induced acute myelocytic leukemia and lung tumors in Wistar rats and n-butylnitrosourea induced acute myelocytic leukemia in MRC-Wistar rats, indicating that B-cell lymphoma induction was specific to the HENU-MRC-Wistar rat model.
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PMID:Effects of 2,4,5-trichlorophenoxyacetic acid, pentachlorophenol, methylprednisolone, and Freund's adjuvant on 2-hydroxyethylnitrosourea carcinogenesis in MRC-Wistar rats. 198 63

White blood cells from a total of 19 patients diagnosed as having acute lymphoblastic (ALL) or acute myeloid (AML) leukaemia were analysed (36 samples) for amplification and expression of the mdr1 and mdr3 genes. Nine of the patients had samples analysed at presentation and at subsequent stages of the disease (24 samples, including 4 at second relapse). Patients received standard MRC UK Trial remission-induction treatment protocols appropriate to disease and age. No amplification of either the mdr1 or mdr3 gene was found in any of the samples, and neither were mdr3 transcripts detected by dot-blot analysis using gene-specific probes. Transcripts of the mdr1 gene were found in only 2 ALL samples (of 10). However, mdr1 transcripts were detected in all AML patients and there was a significant increase in the transcript levels in these patients who went on to first and second relapse, compared with levels measured at presentation (P < 0.001). The results support the hypothesis that P-glycoprotein-mediated drug resistance may be a significant factor in tumour cell resistance to chemotherapy at relapse following initial induction-remission therapy for acute myeloid leukemia.
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PMID:Analysis of MDR1 and MDR3 multidrug resistance gene expression and amplification in consecutive samples in patients with acute leukaemias. 857 59

Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P < 0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and less blood product support. 5-year relapse-free survival (28% v 23%; P = 0.05) and survival (23% v 18%; P < 0.05) were also better with DAT 3 + 10. Post-remission intensification of therapy with MAZE resulted in fewer relapses (66% v 74% at 5 years; P = 0.03) but patients allocated MAZE required considerably more supportive care and 14 (4.5%) died following 312 MAZE courses, whereas no deaths occurred following COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more effective than DAT 1 + 5, even for older patients, but is also less expensive; intensive post-remission therapy with MAZE achieves better leukaemic control but at the cost of substantial toxicity; whereas low-level maintenance therapy confers no apparent advantage in survival as well as being inconvenient and costly.
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PMID:Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party. 875 14

We describe the psychometric analysis of a supplementary quality of life measure (MRC/EORTC QLQ-LEU) for evaluating long term sequelae of leukaemia treatments. The questionnaire under development was administered to 388 patients entered into the EORTC-GIMEMA AML 8A and the MRC AML10 clinical trials who were in complete remission for at least one year after completion of treatment on these trials. Results indicated a measure which is useful in evaluating the long-term effects of treatment in relation to chronic graft-vs-host disease and infection susceptibility. The performance of this measure in terms of its sensitivity and specificity between treatment arms was established by comparisons between the three treatment modalities in the above-mentioned trials and is the subject of further investigation. The new Leukaemia Module can be recommended for use alongside generic QOL instruments as a measure of long-term quality of life in leukaemia trials.
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PMID:A modular questionnaire for the assessment of longterm quality of life in leukaemia patients: the MRC/EORTC QLQ-LEU. 890 62

The relative efficacy and toxicity of the chemotherapeutic agents thioguanine (6TG) and etoposide (VP16) were assessed by a randomized comparison of the DAT (daunorubicin, cytarabine, thioguanine) versus ADE (daunorubicin, cytarabine, etoposide) regimens in the Medical Research Council's 10th acute myeloid leukaemia trial (MRC AML 10), which was open to patient entry from May 1988 to April 1995. In this, the largest reported trial of AML therapy to date, 1,857 eligible patients, mostly less than 56 years old, were randomized: 929 (including 143 children under 15 years old) were allocated to DAT and 928 (143 children) to ADE. The two groups were well matched for presentation features. The complete remission (CR) rate was 81% with DAT and 83% with ADE (P = .3). The percentages of remitters achieving remission after 1, 2, or more than 2 courses were 70%, 22%, and 8% for DAT and 74%, 21%, and 5% for ADE. The percentages failing to achieve a CR due to resistant disease were 11% with DAT versus 9% with ADE (P = .07). There was a slightly higher death rate in CR during consolidation chemotherapy with ADE (9%) than with DAT (6%) (P = .06). Patients receiving DAT took slightly but significantly longer to recover from neutropenia and thrombocytopenia but the median number of days in hospital were similar in each group. ADE patients experienced slightly more severe nonhematologic toxicity. There was also no significant difference between the groups in the longer-term measures of efficacy: disease-free survival at 6 years from CR was 42% (+/-4) for DAT and 43% (+/-4) for ADE (P = .8); relapse rate at 6 years was 50% (+/-4) for DAT and 49% (+/-5) for ADE (P = .6); survival at 6 years was 40% (+/-4) for both DAT and ADE (P = .9). Subgroup analysis failed to show any benefit for etoposide in patients with monocytic or myelomonocytic disease, or in any other diagnostic subgroup. In conclusion, DAT and ADE both achieve high remission rates and good long-term survival, and are equally effective chemotherapy regimens for the treatment of AML patients aged up to 55 years.
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PMID:Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML trial (MRC AML10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council. 911 74

Cytogenetic analysis performed at diagnosis is widely recognised to provide one of the most valuable prognostic indicators in AML. Yet any role for this technique in residual disease assessment, particularly in the context of subsequent transplantation procedures has been incompletely explored. The present study considers the outcome of 190 patients drawn from the UK MRC AML 10 trial in whom cytogenetics were assessed whilst in morphological CR at the time of bone marrow harvest. Cytogenetics at this stage were abnormal in 19 patients (10%). In 11/19 patients, the abnormalities detected reflected the acquisition of new clonal (3/11) or nonclonal changes (8/11) that were not identified at diagnosis; comparison of this group to patients with normal cytogenetics at harvest provided no evidence that such acquired changes are of prognostic significance. In 8/19 patients, abnormalities detected were indicative of persistence of the disease-related clone in harvested marrow. Two of these patients died of sepsis during consolidation therapy. Two received ABMT in first morphological CR: one patient with AML associated with a favourable karyotype (+8,inv(16)) remains in CR, 5.5 years post-transplant, whereas the other with cytogenetic abnormalities considered to confer a poor prognosis (inv(3q),-7), relapsed within 5 months of ABMT. All four of the remaining patients with cytogenetic evidence of persistent disease who were not transplanted in first CR, relapsed within 6.5 months of harvest. Therefore, among 101 of 190 patients with AML characterised by abnormal karyotype at diagnosis, persistence of the disease-related clone in eight patients (8%), revealed by conventional cytogenetic assessment at bone marrow harvest whilst in morphological remission, was found to predict a poor prognosis. Nevertheless, transplantation procedures using marrow which is obviously contaminated with the original leukaemic clone may occasionally still be associated with long-term survival.
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PMID:What happens subsequently in AML when cytogenetic abnormalities persist at bone marrow harvest? Results of the 10th UK MRC AML trial. Medical Research Council Leukaemia Working Parties. 919 55

The MRC UKALL XA trial for patients aged 15 years and over with acute lymphoblastic leukaemia was designed to evaluate short blocks of intensive 'AML-style' treatment. Between 1985 and 1992, 618 eligible patients were entered into the trial. 450 patients were randomized to receive early intensification at 5 weeks, late intensification at 20 weeks, both, or neither. Unlike the concurrent children's trial, UKALL X, which was of similar design, UKALL XA does not demonstrate a clear benefit for intensification, although there was a significant reduction in the relapse risk due to the early block. The estimated increase in disease-free survival at 5 years was 2% with 95% confidence interval from 1% reduction to 5% increase. There may be a real difference between the effect of these treatments in adults and in children, but this result may be somewhat weakened by poorer compliance, with a greater proportion of adults not receiving the treatment arm to which they were randomized.
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PMID:Intensification of treatment for adults with acute lymphoblastic leukaemia: results of U.K. Medical Research Council randomized trial UKALL XA. Medical Research Council Working Party on Leukaemia in Adults. 935 7

359 eligible children with acute myeloid leukaemia (AML) entered the MRC AML 10 trial between May 1988 and March 1995. Patients received four courses of intensive induction and consolidation chemotherapy, with or without subsequent autologous (A-BMT) or allogeneic (allo-BMT) bone marrow transplant. There were randomized comparisons of thioguanine versus etoposide in induction and of A-BMT versus not. Allo-BMT was recommended for patients with a HLA-matched sibling and was evaluated by donor versus no donor comparison. The complete remission rate was 92%. In first remission there were 20 deaths during consolidation chemotherapy and 11 after BMT (8/61 allo-BMTs. 1/60 A-BMTs and 2/4 matched unrelated donor transplants). The relapse rate was low, decreasing from 26% in the first year to 2% in the fourth. Long-term outcome was excellent with survival at 7 years from entry of 56% and event-free survival of 48%. There were no significant differences between thioguanine and etoposide, whereas both A-BMT and allo-BMT reduced relapse risk but did not produce a significant survival benefit. It appears that over half the children entered into AML 10 are cured, a result which compares favourably with other reported series. We conclude that four courses of intensive chemotherapy are an effective approach to the treatment of paediatric AML, which avoids the acute toxicity and long-term side-effects of BMT and also avoids the need for prolonged maintenance therapy or cranial irradiation.
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PMID:Marked improvements in outcome with chemotherapy alone in paediatric acute myeloid leukemia: results of the United Kingdom Medical Research Council's 10th AML trial. MRC Childhood Leukaemia Working Party. 957 93


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