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)

Epidemiological studies have shown an association between cigarette smoking and increased risk of myeloid leukemia in smokers. In evaluating this link it is important to note that cigarette smoke contains benzene, among other carcinogens. Since chronic benzene, among other carcinogens. Since chronic benzene exposure causes acute myeloid leukemia in humans, we aimed to determine the uptake and metabolic activation of benzene from cigarette smoke in smokers by measuring the levels of the urinary benzene metabolite, trans,trans-muconic acid (t,t-MA). The method used involved a clean-up procedure, followed by high-performance liquid chromatography with UV detection. The levels of urinary t,t-MA ranged from 0.02 to 1.3 mg/g creatinine, resulting in a mean of 0.29 +/- 0.04 mg/g creatinine in 42 male smokers, and corresponding values in nonsmokers ranged from "nondetectable" to 0.52 mg/g creatinine with an average of 0.09 +/- 0.02 mg/g creatinine. In the current study, the levels of t,t-MA in smokers were about 3 times higher than those in nonsmokers (P = 0.0001), and a significant correlation between concentration of t,t-MA and levels of cotinine in smokers was observed (r = 0.55; P = 0.0001; 95% confidence interval, 0.30-0.93), suggesting that urinary t,t-MA can be utilized as a biochemical marker to quantitate benzene exposure due to cigarette smoking.
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PMID:Urinary trans,trans-muconic acid as an indicator of exposure to benzene in cigarette smokers. 842 Jun 12

Despite its wellknown adverse effects, Amphoterin B is an integral part of any supportive therapy in haematology/oncology. We report on a thirteen year old boy with acute myelogenous leukemia and suspected fungoid pneumonia. Shortly after iv or inhalative application of Amphotericin B he repeatedly presented with a Raynaud phenomenon of his toes, which ceased after switching to Ambisome (liposomal unilamellar encapsuled Amphotericin B). Since there is evidence that thromboxane A2-mediated arteriolar spasms of renal vessels provoke the wellknown increase in serum creatinine after Amphotericin B, and in different species pulmonal vasoconstriction has been observed, we speculate that a similar mechanism is responsible for the observed Raynaud phenomenon. Thus we suggest inhibitors of prostaglandine synthesis for therapy.
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PMID:[Cyanotic Raynaud phenomenon as a side effect of Amphotericin B]. 890 Nov 82

This review explores the effectiveness and safety of cancer chemotherapy in older individuals and outlines potential guidelines for the management of these patients. Cancer chemotherapy appears less effective in three neoplasms of older individuals: acute myelogenous leukemia, large cell lymphoma, and coelomic carcinoma of the ovary. In the case of acute myelogenous leukemia, a higher prevalence of MDR-1 expression and involvement of the pluripotent hematopoietic stem cells in the neoplastic process contribute to chemotherapy resistance. Chemotherapy-related myelodepression, cardiotoxicity, and peripheral and central neurotoxicity are more common and more severe in older individuals. This toxicity results from the increased vulnerability of target organs and delayed excretion of renally excretable agents. The complications of chemotherapy may be ameliorated by modifying the doses of drugs according to the patient's creatinine clearance, by using antidotes to drug toxicity, and by the early diagnosis and timely management of therapeutic complications. A comprehensive assessment of the older person with cancer allows clinicians to predict the benefits and risks of cancer chemotherapy in individual circumstances.
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PMID:Cancer chemotherapy in the older patient: what the medical oncologist needs to know. 931 85

One hundred and thirteen patients who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic uremic syndrome (HUS). HUS developed in seven patients (four males and three females, five acute lymphocytic leukemia (ALL), one acute myelogenous leukemia, one non-Hodgkin's lymphoma) between 36-196 days after BMT. Four patients were recipients of autologous BMT and three were those of allogeneic BMT. Six patients were preconditioned with the regimens including fractionated total body irradiation (TBI). ALL and preconditioning regimen with TBI were suspected to be the risk factors for the development of HUS. Cyclosporin A (CSP) administration was discontinued in three patients who had been given CSP for graft-versus-host disease prophylaxis. Predonisolone was given to the three patients and plasma exchange was performed in one patient. Both hemolytic anemia and thrombocytopenia were resolved in virtually all patients, while creatinine elevation has persisted along with hypertension in one patient.
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PMID:[Hemolytic uremic syndrome after bone marrow transplantation]. 969 69

During remission induction chemotherapy, a 41-kDa cleavage product of alpha1-antitrypsin (alpha1-AT41) can be found in the urine of patients with acute myeloid leukemia. By using immunoblotting with antibodies against this protein, 27 patients with acute myeloid leukemia were screened for the excretion of this fragment and the amount of alpha1-AT41 compared with treatment response assessed by therapy-induced cytoreduction in the bone marrow and time to reach remission. Patients with acute lymphoblastic leukemia, malignant lymphomas, and solid tumors receiving chemotherapy, patients with nonmalignant diseases like sepsis and kidney dysfunction, and healthy subjects were probed to evaluate the specificity of this phenomenon. In 74% of the acute myeloid leukemia patients, the truncated inhibitor was detected. Mean concentration of peak excretion was found to be 6.7 microgram/mg creatinine (range, 1.1-41 microgram/mg). Among the patients treated with induction chemotherapy, those who responded completely (<5% residual marrow blast cells) exhibited significantly higher alpha1-AT41 concentrations than the nonresponders (P < 0.03). Patients who showed a partial response (6-25% residual blasts) excreted intermediate values of the protein. The probability of median time to reach remission was 40 days in patients excreting the truncated inhibitor in measurable amounts compared to 100 days in patients negative for alpha1-AT41 (P < 0.02). The 41-kDa fragment was also found in one of 10 patients with acute lymphoblastic leukemia and in 3 of 18 lymphoma patients but not in those with solid tumors, infections, or kidney disease or in healthy individuals.
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PMID:Urinary excretion of proteolyzed alpha1-antitrypsin: specificity, quantitation, and relation to therapy response in patients with acute myeloid leukemia. 981 74

To determine whether the addition of lisofylline (LSF) to idarubicin (12 mg/m2 daily x 3) + ara-C (1.5 g/m2 daily x 4) affects the rates of infection, serious infection, CR or mortality during remission induction of newly diagnosed AML, RAEB-t or RAEB, we randomized 70 patients to 3 mg/kg lisofylline or placebo every 6 h i.v., to begin 6 h before the first dose of idarubicin and to continue until recovery of neutrophil and platelet counts or for 28 days, whichever came first. Eligibility required that patients be below age 71 years, have no history of abnormal counts, or chemotherapy for a prior malignancy, and have a creatinine <1.6 mg/dl and bilirubin <3.0 mg/dl. The study was double-blinded and infections were tabulated separately and independently at MD Anderson and by a three-member outside panel of experts. Logistic regression was used to assess the relative effects of treatment arm (LSF or placebo), age, performance status, treatment site (laminar air flow room or not), and cytogenetics on rates of infection and serious infection following the first course of chemotherapy, and on CR rate. There were 84% and 87% concordance between the expert panel and MD Anderson enumerations of infection and serious infections, respectively. Both analyses found no significant (P < 0.05) differences between the rates of infection, or serious infection, in the placebo and LSF groups. CR, 60-day, and overall mortality rates were similar in the two groups, as were time to neutrophil and blood count recovery and outcome once in CR. Logistic regression analyses supported the above conclusions. Severe nausea/vomiting and mucositis were more frequent in the LSF group. Our results suggest that larger studies of LSF in newly diagnosed AML, RAEB-t, or RAEB are not warranted.
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PMID:Treatment of newly diagnosed AML, RAEB-t or RAEB with lisofylline or placebo in addition to chemotherapy. 1036 Mar 71

Dysregulation of apoptosis is an important mechanism in leukemogenesis. Caspases are cysteine proteases that play a major role in the activation of apoptotic pathways and chemotherapy-induced cell death. High levels of inactive, uncleaved caspase 2 and caspase 3 have recently been associated with poor survival in patients with acute myelogenous leukemia. We hypothesized a similarly significant role for caspase 2 and caspase 3 in patients with acute lymphoblastic leukemia. We determined levels of uncleaved caspase 2 and caspase 3 by quantitative Western blot analysis in peripheral blood samples of 45 adults with newly diagnosed ALL. We evaluated patient prognostic variables and caspase levels using multivariate logistic and Cox regression models to determine their impact on complete remission rate and overall survival probability. Levels of caspase 2 and, to a lesser degree, caspase 3 were highly associated with cytogenetic abnormalities, with lower levels in the diploid group (P = 0.016 and P = 0.10, respectively). No association between either caspase level and the percentage of bone marrow blasts was found. A high level of caspase 3 (>0.37 as determined graphically) was significantly associated with achieving complete remission (CR; P = 0.006). A multivariate logistic regression analysis including age, WBC count, percentage of peripheral and marrow blasts, hemoglobin, albumin, lactate dehydrogenase, bilirubin, and creatinine determined that a high level of caspase 3 was the most significant predictor of CR (P = 0.025, adjusted), with albumin the only other significant variable (P = 0.031). Caspase 2 levels were not associated with probability of CR. In a multivariate Cox model for survival, however, levels of caspase 2 above 0.37 were associated with a lower survival probability than were levels below that threshold (P = 0.064). High levels of caspase 3 may have a significant effect on achieving CR. Because of the limited power (n = 45) of our study, the significance of caspase 2 and caspase 3 on overall survival remains to be validated by further investigations.
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PMID:Caspase 2 and caspase 3 as predictors of complete remission and survival in adults with acute lymphoblastic leukemia. 1063 37

The concentration of selenium in serum was measured by the neutron activation method in three groups of children: 30 healthy children, 20 children with Acute Myeloblastic Leukemia (AML) and 40 with Acute Lymphoblastic Leukemia (ALL) (L1; n = 20, L2; n = 20). The samples were taken before and after induction chemotherapy. Age, sex, FAB, initial WBC, BUN, creatinine and urinary analysis did not show a significant change in the amount of selenium in serum. Selenium concentration in serum samples of ALL children before chemotherapy showed no significant differences as compared with that of normal individuals, but there were significant differences between children with AML and normal individuals (76.46 +/- 24.59 micrograms/L vs 102.38 +/- 19.25 micrograms/L, with p < 0.02). In conclusion, the question of whether these deficiencies are responsible for the disease or are the result of a secondary effect of the cancer remain to be answered. Immediately after induction chemotherapy, the selenium concentration in the serum of ALL children decreased significantly (80.14 +/- 15.48 micrograms/L vs 110.72 +/- 28.3 micrograms/L, p < 0.001), but this was not the case for AML children. These findings may be due to the difference in the drugs administered in induction chemotherapy of ALL and AML children.
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PMID:Determination of selenium in blood serum of children with acute leukemia and effect of chemotherapy on serum selenium level. 1070 48

In order to characterize clinical and biological characteristics of elderly patients with acute myelogenous leukemia (AML), we retrospectively analysed 83 elderly patients aged 60 years or more and, as a control, 114 younger patients aged 15 to 59 years who were admitted to our hospital between August 1984 and January 1998. There was a significantly higher incidence of preceding myelodysplastic syndromes in the elderly patients. They also had a significantly higher incidence of unfavorable cytogenetic abnormalities (loss or partial deletion of chromosome 5 or 7) and a significantly lower incidence of favorable cytogenetic abnormalities, such as t(15:17), t(8:21), or inv(16). With regard to FAB subtypes in de novo AML, the incidence of M3 subtype was significantly lower in the elderly group. Myeloperoxidase positivity of AML cells in the elderly group was lower than that in the younger group. Laboratory data at presentation disclosed a lower peripheral leukemic cell count, a higher fibrinogen level, a lower serum protein level, and a higher serum creatinine level in the elderly group. They also had poorer performance status and more frequent concomitant diseases at presentation, including liver diseases, heart diseases, or documented infections. It was concluded that elderly AML patients 60 years or older had a higher incidence of poor prognostic factors compared to younger patients.
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PMID:[Retrospective study of acute myelogenous leukemia in 83 elderly patients: clinical and biological characteristics]. 1084 59

An 18-year-old woman was admitted to hospital because of subcutaneous hematoma and fever of unknown origin. Acute myeloid leukemia was diagnosed and empirical antimicrobial treatment and induction chemotherapy were started. After initial defervescence, fever relapsed 2 days after the onset of neutropenia. The CT scan of the lung was consistent with an invasive fungal infection. Treatment with amphotericin B was started and antimicrobial treatment was continued with liposomal amphotericin B because of an increase in creatinine later. The fever persisted and the patient suddenly developed progressive neurological symptoms. CT scan of the head suggested cerebral infarction and angiography of the extra- and intracranial arteries showed signs of vasculitis. Six days after the onset of neurological symptoms cerebral death was diagnosed. Autopsy revealed non-septate, irregularly branched hyphae in various histologic sections including brain. Absidia corymbifera could be isolated from lung tissue confirming the diagnosis of disseminated mucormycosis. In this case, angiographic findings suggested severe cerebral vasculitis which was in fact caused by thromboembolic dissemination of fungal hyphae. This case underlines the fact that cerebral symptoms in febrile neutropenic patients are highly indicative for fungal infections of the brain.
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PMID:Disseminated mucormycosis caused by Absidia corymbifera leading to cerebral vasculitis. 1096 35


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