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)

The use of in-vitro culture methods for studying human haemopoietic cells has advanced greatly since 1970. These methods have contributed to our understanding of the mechanisms controlling granulopoiesis though the physiological role of colony-stimulating factor needs further clarification. In leukaemia they offer an approach to the study of possible causal factors and to the characterisation of leukaemic-cell defects. Results already obtained support the concept that the bone-marrow in acute myeloid leukaemia consists of coexisting populations of normal and leukaemic cells, with a leukaemic clone predominating in relapse and normal clones regenerating in remission. For the individual patient, in-vitro methods may prove useful in assessing prognosis and in confirming the completeness of remission; the detection of early relapse may then indicate the need for changing or re-instituting therapy. Further studies may aid the classification of the "preleukaemic" states and may help in the identification of the various causes of neutropenia.
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PMID:Clinical applications of bone-marrow culture. 5 63

A series of 24 patients with severe neutropenia, most of whom had acute myeloblastic leukemia, were treated in an isolation unit with oral nonabsorbable antibiotics and were compared to 21 similar patients receiving oral antibiotics alone. The frequency of bacterial infections was lower in the patients receiving both isolation and oral antibiotics compared to the patients who received only oral antibiotics. The responses to chemotherapy in terms of remission rates were identical for the two groups.
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PMID:Comparative randomized study of protected environment plus oral antibiotics versus oral antibiotics alone in neutropenic patients. 10 63

Twenty-seven patients receiving a standard cytosine arabinoside and daunorubicin regimen as induction of reinduction therapy of acute myelogenous leukemia were randomly assigned to receive lithium carbonate, 300 mg t.i.d., or no lithium. Treatment groups were comparable with respect to age and baseline granulocyte counts. All patients developed granulocyte nadirs below 100/cu mm. By actuarial analysis, the median duration of granulocytopenia, less than 1000/cu mm, was 16.0 days in the lithium group and 24.6 days in the no-lithium group, p = 0.013. The median duration of granulocytes less than 500/cu mm also favored the lithium group but only approached statistical significance: 14.0 days versus 20.5 days, p = 0.054. Lithium levels between 0.5 and 1.0 meq/liter were easily maintained in 11 of 12 patients receiving lithium, 300 mg t.i.d., and toxicity directly attributable to lithium was not observed. Despite the shortened duration of neutropenia, the incidence of infections and the rate of remission were not affected.
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PMID:Lithium and granulocytopenia during induction therapy of acute myelogenous leukemia. 28 86

VP-16-213, a semisynthetic podophyliotoxin, was tested for antitumor and clinical toxicity in 126 children. The drug was administered iv daily x 5 days every 2 weeks at a starting dose of 75 mg/m2/day. The dose was increased by 25 mg/m2/day/course until clinical response or significant toxicity occurred. The only major toxicity was hematologic, with neutropenia as the most predominant feature. There was one local allergic reaction at the site of injection. No systemic allergic responses were reported. The drug demonstrated significant activity in acute myelomonocytic leukemia with four responses among 19 patients, less activity in acute myelocytic leukemia with two responses among 44 patients, and little activity in acute lymphocytic leukemia with only one partial response among 12 patients. Objective partial responses occurred in ten of 48 patients with solid tumors: two each with Wilms' tumor, lymphoma, and histiocytosis X, and one each with rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma, and undifferentiated carcinoma. The inclusion of VP-16-213 in combination chemotherapy for childhood acute myelomonocytic leukemia and acute myelocytic leukemia appears indicated in patients relapsing after initial therapy. For solid tumors this is an interim report, with further patient accrual required before specific comments can be made.
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PMID:Phase II study of VP-16-213 in childhood malignant disease: a Children's Cancer Study Group Report. 29 6

The effect of granulocyte transfusions on the course of infection in patients under treatment for acute leukemia was evaluated by comparing 19 febrile episodes in 15 patients receiving antibiotics alone with 18 febrile episodes in 13 patients receiving antibiotics in combination with granulocyte transfusions from ABO-matched donors. Both groups had a similar age, sex distribution and duration of disease prior to the febrile episode. About two-thirds of the patients in both groups had acute myeloblastic leukemia. 94% of the patients in the transfused group and 74% of the control group survived the febrile episode. In patients with positive blood cultures all transfused patients survived as compared to only 57% in the control group (p=0.05). In patients with persistent bone marrow failure 92% of the transfused patients survived as compared to 73% in the control group. Granulocyte transfusions had no effect on the outcome of febrile episodes in patients with negative blood cultures or early recovery of marrow function. These data appear to support the contention that granulocyte transfusions are beneficial in patients with blood culture-proved sepsis with persistent neutropenia.
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PMID:Granulocyte transfusion therapy: a clinical trial in patients with acute leukemia and sepsis. 34 23

VM-26, a semisynthetic podophyllotoxin, was tested for antitumor activity and clinical toxicity in 181 children. The drug was administered iv at weekly intervals, beginning at a dose of 130 mg/2/week. The dose was increased, as tolerated, after 3 and 6 weeks to 150 and 180 mg/m2/week, respectively. The only major toxicity was hematologic, with neutropenia predominating. Anaphylaxis occurred in one patient. The drug demonstrated significant activity in acute lymphocytic leukemia (four responses among 15 patients) and neuroblastoma (ten responses among 31 patients). Objective responses were also noted in one patient each with acute myelogenous leukemia, Hodgkin's disease, histiocytic lymphoma, Wilms' tumor, Ewing's sarcoma, undifferentiated carcinoma, and sacrococcygeal sarcoma. Further trials of VM-26 in these childhood malignancies are warranted.
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PMID:Phase II study of VM-26 in acute leukemia, neuroblastoma, and other refractory childhood malignancies: a report from the Children's Cancer Study Group. 38 Aug 3

Approaches to the diagnosis and classification of preleukemic states involving chronic cytopenias are presented and discussed. Diagnosis of these states is facilitated by the identification of anomalies in all the myeloid cell lines (i.e., those derived from the bone marrow). These cellular anomalies may be morphologic, biochemical, or functional in nature or may affect the quantity of cell in each line in the bone marrow and the peripheral blood. Such anomalies may occur alone or may be associated. A tentative classifiction is proposed which is based on one or several of these anomalies. Among the quantitative criteria of classification is a moderate and static excess of myeloblasts and promyelocytes in the bone marrow. Refractory anemia with an excess of myeloblasts (RAEM) in the most frequent of these states. Its main clinical and hematologic features are described. The disease course is quite typical, the mean survival being 20 months; some patients survive for more than 30 months. Acute myeloid leukemia (AML) was the cause of death in less than 28% of cases. Infection in the absence of severe neutropenia was frequent. The relationship between RAEM and AML is disc,ssed, and the individual characteristics of RAEM are emphasized.
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PMID:Preleukemic states. I. Definition and classification. II. Refractory anemia with an excess of myeloblasts in the bone marrow (smoldering acute leukemia). 100 6

Colony stimulating factors (CSFs) are glycoprotein hormones that regulate growth and differentiation of hematopoietic progenitor cells. Their use to stimulate granulocyte precursors during periods of neutropenia in patients with acute myeloid leukemia (AML) is limited by their concomitant stimulation of the proliferation of myeloblasts. The effects of these agents on leukemic lymphoblasts is not entirely known. We have investigated the in vitro effects of granulocyte-CSF (G-CSF) and granulocyte/macrophage-CSF (GM-CSF) on leukemic cells from children with acute lymphoblastic leukemia (ALL). DNA synthesis of bone marrow cells from 22 children with ALL, either at diagnosis or in relapse, was examined with and without CSFs. Proliferative potential was also tested in a clonogenic assay with 13 bone marrow specimens. These factors did not stimulate the growth of ALL cells in either assay. Our results indicate that G-CSF and GM-CSF should be able to stimulate granulocyte proliferation without enhancing leukemic proliferation during periods of neutropenia in children with ALL.
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PMID:The effect of recombinant GM-CSF and G-CSF on the bone marrow cells of children with acute lymphoblastic leukemia. 127 25

Levels of serum granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with various leukocyte disorders were estimated by enzyme-linked immunosorbent assay (ELISA). Some cases of acute myelogenous leukemia and aplastic anemia showed elevated serum levels of G-CSF and/or GM-CSF, whereas almost all of 23 healthy controls showed G-CSF and GM-CSF levels lower than 100 pg/ml. High levels of both types of CSF were noted in patients with granulocytosis due to infection. These levels became lower after resolution of the infection. Daily changes in serum CSF levels were also examined in a patient with autoimmune neutropenia, and it was found that the peripheral neutrophilic granulocyte count changed almost in parallel with the serum G-CSF level but not with GM-CSF, following the pattern with a delay of about 4-5 h, suggesting the possibility that G-CSF mainly regulates peripheral neutrophil circulation.
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PMID:Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions. 137 27

Etoposide has been used in the treatment of a wide variety of neoplasms, including small cell lung cancer. Kaposi's sarcoma, testicular cancer, acute leukemia, and lymphoma. Its current therapeutic use is limited by myelosuppression, particularly neutropenia. Pharmacodynamic studies of etoposide show that this toxicity can be modeled using a modified Hill equation, and that the dose intensity of etoposide can be successfully increased by adaptive control using this model. Significant influences on the degree of myelosuppression include pretreatment leukocyte count, performance status, extent of prior erythrocyte transfusions, and serum albumin level. In the past 5 years, interest has developed in a distinct subset of acute nonlymphocytic leukemia that is associated with prior exposure to etoposide. This syndrome has been described in several studies, and is characterized by the lack of a preleukemic phase, M4 or M5 morphology, and distinct translocations involving the chromosome 11q23 region.
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PMID:New perspectives on the toxicity of etoposide. 149 30


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