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)

With respect to the enzymes of NADPH-forming metabolic pathways in human leukocytes: (a) Glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) were less active in leukocytes (mostly myeloblasts) from eight patients with acute myeloblastic leukemia (I) than in leukocytes (mostly granulocytes) from 16 normal subjects (II). (b) Of the enzymes of the citrate cleavage pathway, ATP citrate lyase and malate dehydrogenase (decarboxylating) (NADP+) were virtually absent in the cells studied. (c) Isocitrate dehydrogenase (NADP+), aspartate aminotransferase, and alanine aminotransferase, which, together with the much more active malate dehydrogenase, constitute a newly proposed NADPH-forming metabolic cycle, showed a higher activity in I than in II or III, and therefore could compensate, as concerns NADPH-generation, for the low activity of pentose cycle dehydrogenases. We are not sure whether the enzymatic characteristic of I cells is attributable to their immaturity or to their leukemic nature.
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PMID:Enzyme activities of NADPH-forming metabolic pathways in normal and leukemic leukocytes. 23 46

Forty-three patients with hematopoietic disease were treated with intensive chemotherapy and radiotherapy, followed by allogeneic bone marrow transplantation (BMT) from 28 HLA-identical and 10 one to two antigen haploidentical sibling donors and autologous BMT (5 cases). Of these cases, there were 21 with acute nonlymphocytic leukemia (ANLL), 5 with acute lymphocytic leukemia (ALL), 6 with chronic myelocytic leukemia (CML), 2 with Hodgkin's disease (HD), 8 with severe-form aplastic anemia (SAA) and 1 with thalassemia. Complications of BMT were evaluated including acute graft-versus-host disease (GVHD), interstitial pneumonia (IP), veno-occlusive liver disease (VOD), abnormalities of liver function (LF), and alteration of hepatitis B virus (HBV) markers. In thirty-three patients who were followed up for more than 3 months, we found that the incidence of moderate to severe acute GVHD (9.1%) and IP (two cases, 4.7%) were low. No VOD occurred in our series. During the follow-up period, 27 out of 35 patients (77%) had high alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, even up to 1000 U/liter; however, only one patient succumbed to a hepatitis-related complication. Previous hepatic damage from HBV infection before BMT does not appear to increase the risk of posttransplant morbidity and mortality.
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PMID:Complications of bone marrow transplantation in Chinese. 232 72

We describe 5 cases of fulminant hepatitis caused by the HBV infection in patients with haematological diseases, mostly malignancies (ALL, lymphoma, aplastic anemia, AML) following intensive chemotherapy. Infection was confirmed by serological examination (HBsAg positivity) and by electron microscopy (viral particles). After termination of chemotherapy fulminant hepatitis developed with hepatic failure and very high levels of AST and ALT. Autopsy revealed massive necrosis without signs of regeneration. We suggest that immunosuppressive therapy increases the risk of severe infection of hepatocytes with HBV and subsequent withdrawal of chemotherapy causes "immunological rebound" leading to massive necrosis.
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PMID:Fulminant hepatitis caused by a hepatitis B virus infection in the patients with haematologic malignancies. Report of 5 cases. 943 99

Recent reports using historical controls or registry cohorts suggest, respectively, either an increase in the mortality or a decrease in the incidence of hepatic veno-occlusive disease (VOD) with the administration of intravenous immunoglobulin (i.v.Ig) after bone marrow transplantation. These divergent results prompted us to conduct a retrospective analysis of two randomized clinical trials conducted at our center to determine the effect of i.v.Ig infusions on the development and severity of VOD. Patients were randomized to receive (n=318) or not to receive (n=315) i.v.Ig prophylaxis after human leukocyte antigen-identical sibling (n=414), mismatched or unrelated (n=178), or autologous or syngeneic (n=41) marrow transplantation. To determine the relationship of i.v.Ig to the development and severity of VOD, a single observer reviewed data displays created for each patient for grading VOD without knowledge of patient i.v.Ig use. In this analysis, VOD was defined as hyperbilirubinemia > or =2.0 mg/dL before day 20 and abrupt weight gain > or =2% before day 14 posttransplant in the absence of other causes of liver disease. Hepatic VOD developed in 235 (37%) of the 633 randomized patients. No evidence for VOD was found in 230 (36%) patients. The remaining 168 (27%) patients were classified as having liver disease of uncertain etiology. Hepatic VOD was judged to be severe in 63 (10%) and mild or moderate in 172 (27%) patients. The number of patients developing any VOD or severe VOD was similar between those randomized to i.v.Ig prophylaxis and untreated controls (115 vs. 120 and 32 vs. 31, respectively). Logistic regression models identified several covariates as significant (p < 0.01) factors associated with the development of severe VOD. Increased risk occurred with elevated pretransplant serum aspartate aminotransferase (odds ratio [OR] = 2.64) and earlier year of transplant (OR = 3.73); decreased risk occurred with autologous or twin donors (OR = 0.09) and acute myeloid leukemia (OR = 0.39). The development of any VOD was associated with an elevated pretransplant alkaline phosphatase (OR = 4.1), pretransplant use of vancomycin (OR = 1.6) or amphotericin (OR = 3.0), posttransplant use of cyclosporine (OR = 2.5), older patient age (OR = 1.03), and obesity (OR = 0.78). We concluded from the controlled trials of 633 patients that the administration of i.v.Ig did not influence the development or severity of VOD after bone marrow transplantation.
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PMID:Intravenous immunoglobulin and the risk of hepatic veno-occlusive disease after bone marrow transplantation. 970 88

A 42-year-old man was admitted with heavy retrosternal pain lasting 30 min. Electrocardiography showed typical signs of acute anterior myocardial infarction. The patient reported only attacks of coughing for a couple of days, and no serious diseases. The physical examination was normal. Laboratory tests showed a white blood cell count of 45/nl, platelet count of 58/nl, and hemoglobin of 14.4 g/dl. Blood chemistry showed elevated lactic dehydrogenase (413 U/l) but no elevation in creatine phosphokinase or glutamic-oxaloacetic transaminase. Therefore no thrombolysis was administered, but coronary angiography was performed. This showed a long-distance, subtotal thrombotic occlusion of the left anterior descending artery. After percutaneous transluminal coronary angioplasty and implantation of serial stents a normal perfusion of the artery was observed. The patient's blood and bone marrow films revealed acute myeloid leukemia FAB M2. Various conditions can cause a myocardial infarction in leukemias. We discuss the clinical management and the possible reasons for a subtotal thrombotic occlusion of the coronary artery.
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PMID:Acute anterior myocardial infarction as first manifestation of acute myeloid leukemia. 1175 28

A 77-year-old man with pneumonia associated with acute myeloid leukemia was introduced to the hepatology unit at our hospital for hyperbilirubinemia. He had been suffering from a high fever because of pneumonia. He was icteric and his serum concentrations of total and direct bilirubin were 13.1 and 7.9 mg/dl, respectively. However, the other standard biochemical examinations for hepatic function, such as serum concentrations of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase were normal except for lactate dehydrogenase. Lactate dehydrogenase isoenzyme analysis revealed that the high concentration was derived from leukemia cells. Ultrasonography of the abdomen revealed no abnormality in the liver or biliary tract. Administration of antibiotics for pneumonia decreased the serum bilirubin concentration, however, he died because of respiratory failure caused by the progression of pneumonia at 33 days after the admission. It was suggested that a disturbance in the bilirubin metabolism without hepatocyte necrosis or mechanical cholestasis might be involved in the pathogenesis of hyperbilirubinemia in patients with infectious diseases.
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PMID:Unusual hyperbilirubinemia associated with bacterial pneumonia and acute myeloid leukemia. 1280 38

DT388GMCSF, a fusion toxin composed of the NH2-terminal region of diphtheria toxin (DT) fused to human granulocyte-macrophage colony-stimulating factor (GMCSF) has shown efficacy in the treatment of acute myeloid leukemia. However, the primary dose-limiting side effect is liver toxicity. We have reproduced liver toxicity in rats using the rodent cell-tropic DT-murine GMCSF (DT390mGMCSF). Serum aspartate aminotransferase and alanine aminotransferase were elevated 15- and 4-fold, respectively, in DT390mGMCSF-treated rats relative to controls. Histologic analysis revealed hepatocyte swelling; however, this did not lead to hepatic necrosis or overt histopathologic changes in the liver. Immunohistochemical staining showed apoptotic cells in the sinusoids, and depletion of cells expressing the monocyte/macrophage markers, ED1 and ED2, indicating that Kupffer cells (KC) are targets of DT390mGMCSF. In contrast, sinusoidal endothelial cells seemed intact. In vitro, DT390mGMCSF was directly cytotoxic to primary KC but not hepatocytes. Two related fusion toxins, DT388GMCSF, which targets the human GMCSF receptor, and DT390mIL-3, which targets the rodent IL-3 receptor, induced a less than 2-fold elevation in serum transaminases and did not deplete KC in vivo. In addition, DTU2mGMCSF, a modified form of DT390mGMCSF with enhanced tumor cell specificity, was not hepatotoxic and was significantly less toxic to KC in vivo and in vitro. These results show that DT390mGMCSF causes liver toxicity by targeting KC, and establish a model for studying how this leads to hepatocyte injury. Furthermore, alternative fusion toxins with potentially reduced hepatotoxicity are presented.
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PMID:Diphtheria toxin-murine granulocyte-macrophage colony-stimulating factor-induced hepatotoxicity is mediated by Kupffer cells. 1563 63

New treatments for relapse of acute myeloid leukaemia (AML), include gemtuzumab ozogamicin (GO), an anti-CD33 monoclonal antibody. We describe a second case of GO-induced sinusoidal obstructive syndrome (SOS) effectively treated with defibrotide (DF). No stem-cell transplantation was involved. On day 23 after the first GO dose, a patient presented with ascites, weight gain, liver enlargement and pain in the right upper quadrant. Sudden hepatic cytolysis (transaminases at six times the normal range: grade 3) and cholestasis [alkaline phosphatase ALP and gamma-glutamyltransferase (GGT) respectively at four and eight times the normal range: grade 2] were observed but there was no evidence of increase serum bilirubin. Treatment with DF (Prociclide), Crinos; 10 mg/kg/day, or 200 mg, q.i.d.) improved the hepatic abnormality within a few days (serum transaminases decreased from 312 to 103 IU/L for aspartate aminotransferase (AST) and from 141 to 80 IU/L for alanine aminotransferase (ALT) within 3 days ALP increased from 253 to 383 IU/L and gamma-GT from 238 to 417 IU/L 4 days after administration of DF. The clinical and biological features of our case suggest a direct involvement of GO in causing SOS, even when used as monotherapy, without allogenic stem-cell transplantation. Low dose DF (10 mg/kg/day) given early during the development of SOS associated with GO was effective. Unfortunately, in our case the patient eventually died of multi-organ failure probably because of failure of GO.
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PMID:Gemtuzumab ozogamicin-induced sinusoidal obstructive syndrome treated with defibrotide: a case report. 1688 10

To evaluate the liver function, splenomegaly and related factors in the newly diagnosed acute leukemia patients. One hundred of fifty eight acute leukemia patients admitted in our hospital from March 2003 to April 2006 were studied. The related factors such as peripheral WBC count, bone marrow blasts, peripheral blasts, sex, age, AML, ALL affecting the liver function and splenomegaly were evaluated. Sixty two (39.24%) patients presented with splenomegaly. Twelve (7.59%) patients presented with hepatomegaly. Serum ALT was elevated in 54 (34.17%) patients. Similarly, serum AST, GGT, ALP, and Direct bilirubin were elevated in 26 (16.45%), 32 (20.25%), 20 (12.65%), and 22 (13.92%) patients, respectively. Low serum albumin was found in 40 (25.31%) patients. PT was prolonged in 62 (39.24%) patients. Statistical study shows that there is a relation between high WBC counts and elevated serum ALT (P<0.05) and high WBC counts and splenomegaly (P<0.05). Acute leukemia patients with leukocytosis are more prone to develop abnormal liver function and splenomegaly.
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PMID:Abnormal hepatic function and splenomegaly on the newly diagnosed acute leukemia patients. 1834 Mar 67

The application of myeloablative Allo-SCT is limited by its associated morbidity and mortality. Reduced-intensity conditioning regimens attempt to diminish these, but are associated with a higher risk of disease relapse. Given the evidence of activity of clofarabine and cytarabine in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), we explored a novel reduced-intensity conditioning regimen based on this backbone. Patients received clofarabine 40 mg/m(2) i.v. on days -6 to -2, cytarabine 1 g/m(2) i.v. on days -6 to -2 and anti-thymocyte globulin (ATG) 1 mg/kg on day -4 and 2.5 mg/kg x 2 days on days -3 and -2. Seven patients were enrolled. Their median age was 54 years; three were with MDS and four with AML. The median duration of neutropenia was 14 days and that of thrombocytopenia was 22 days. Toxicities included hand-foot syndrome (57% grade 2), elevated alanine aminotransferase (ALT) (57% grade 3), elevated aspartate aminotransferase (AST) (86% grade 3) and hyperbilirubinemia (29% grade 3-5). No acute GVHD was observed. Enrollment to the trial was halted after three of the first seven patients expired on days +15, +26 and +32. Three of the four surviving patients have relapsed with a median TTP of 152 days. This regimen was not sufficiently immunosuppressive to ensure engraftment, and was associated with substantial morbidity and mortality.
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PMID:Allo-SCT conditioning for myelodysplastic syndrome and acute myeloid leukemia with clofarabine, cytarabine and ATG. 1913 40


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