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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes the use of the bromodeoxyuridine/propidium iodide method to assess the effects of bioactive and cytotoxic agents on the kinetic characteristics of acute myelogenous leukemia cells. By careful selection of gates, the following parameters can be measured simultaneously using only 50,000 cells: the proportion of cells in S-phase, the distribution of cells within the S-phase compartment, the relative rate of DNA synthesis, the relative distribution of S-phase times, the proportion of S0 cells, and the proportion of cells in G1 and G2/M. This method was used to demonstrate that while retinoic acid, alpha-interferon, and cytosine arabinoside may all "inhibit" DNA synthesis, the actual effects of these agents differ. Retinoic acid appears to arrest cells in G1 without affecting the rate of DNA synthesis, while alpha-interferon and cytosine arabinoside "inhibit" DNA synthesis by reducing the rate of synthesis per se.
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PMID:Multiparameter assessment of the cell cycle effects of bioactive and cytotoxic agents. 163 20

One proposed therapeutic application of granulocyte colony-stimulating factor (G-CSF) is in differentiation induction therapy of myelodysplastic states (MDS) or acute myeloid leukemia (AML). G-CSF however has a substantial growth including effect which limits its potential as a differentiation inducing agent. We have therefore made a systematic search for agents which might restrain the proliferative effects of G-CSF whilst retaining the differentiation stimulus. Of all the agents we have tested on human bone marrow progenitor cells: (6-thioguanine, all-trans retinoic acid, vincristine, recombinant human alpha-2b and gamma-interferon) only the latter abolished the stimulation of cell growth and retained, or possibly increased, the differentiation effect of G-CSF. The antiproliferative drugs 6-thioguanine and vincristine both antagonized the neutrophil-granulocyte differentiation inducing action of G-CSF. Retinoic acid and alpha-2b interferon both had weak effects on proliferation and failed to enhance differentiation. These results suggest that it may be possible, by combining G-CSF with a suitable second agent, to utilize its substantial differentiation inducing effect without incurring the potentially hazardous effects of increased leukemic cell growth.
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PMID:Dissociation of the proliferation and differentiation stimuli of granulocyte colony-stimulating factor (G-CSF). 169 Mar 19

Alpha-interferon (IFN) may inhibit the proliferation of human leukemic progenitor cells (L-CFU) in vitro and enhance the anti-tumor effects by heat. In this study, the combined effects of IFN and hyperthermia on the growth of L-CFU and human granulocyte-macrophage progenitors (CFU-GM) were examined to determine if this combination resulted in a greater selective killing of L-CFU than that obtained by heat treatment alone. The survival of normal CFU-GM without IFN decreased at elevated temperatures (42-44 degrees C). However, IFN added during heating (42 and 43 degrees C) appeared significantly to protect against the hyperthermic killing of CFU-GM in vitro leaving over 50% of CFU-GM surviving. The optimal dose to protect CFU-GM in vitro dropped to a rather low dose (100 U/ml). On the other hand, the addition of IFN to leukemic cell suspensions enhanced the hyperthermic killing of myeloid leukemic cell lines (HEL and KG-1) as well as a T lymphoblastic cell line (CEM) in a dose-related manner. In addition, similar results were observed in the study of L-CFU from patients with acute myelogenous leukemia. These results suggest that IFN can be used to broaden the difference between surviving fractions of CFU-GM and L-CFU by heat. Thus, this combination could be applied effectively and safely for the elimination of residual clonogenic leukemic cells in autologous remission marrow graft before autologous bone marrow transplantation.
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PMID:Alpha-interferon broadens the difference between surviving fractions of normal and leukemic progenitor cells in vitro by heat: its application to marrow purging. 175 27

Post-transfusion hepatitis (PTH) is a major problem in patients with acute leukemias requiring blood products during induction or consolidation therapy. In fact, PTH causes delays of chemotherapy with major violations in the timing of protocols. In order to assess the efficacy and safety of a short course of alpha-interferon (alpha-IFN) in inducing early remission of PTH, we treated seven patients who developed acute hepatitis during a post-remissional phase of AML. Patients received 3 MU of alpha-IFN i.m. three times weekly for one month. One patient stopped alpha-IFN at 2 weeks because of severe itching, after ALT normalization. Five out of 6 subjects normalized ALT within a mean time of two weeks. Minor side effects were observed in 2 cases. Three patients relapsed within eight weeks after stopping alpha-IFN. They underwent a second remission upon treatment with the same schedule. All patients continued their treatment protocol for AML without delay.
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PMID:Recombinant interferon alpha-2B for acute post-transfusion hepatitis in acute myeloid leukemia. 180 50

108 consecutive patients with de novo acute myeloid leukaemia at ages 15 to 59 years were treated in a prospective controlled multicentre trial. Induction with combination TAD resulted in a complete remission in 85 cases (79%). After a cyclic consolidation programme for 6 months, 73% of the remissions continued. The maintenance therapy was at random either nothing, or alpha interferon, or monthly 5 day courses with thioguanine and cytarabine. The median duration of all remissions was 13 months; that of those in the control and interferon arms 15 months each, and in the chemotherapy arm 18 months. The median survival of all the 108 patients was 16 months; that of those in the control arm 20 months, in the interferon arm 33 months and in the chemotherapy arm 26 months. At 5 yr, 31%, 22% and 31%, respectively, were alive. The survival curves did not differ from each other significantly. Maintenance treatment after an intensive induction and a moderately intensive consolidation was of no benefit in this study. Interferon did not improve the prognosis.
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PMID:Value of maintenance therapy with chemotherapy or interferon during remission of acute myeloid leukaemia. 191 7

Recently recombinant cytokines have been used to treat hematological malignancies. The potential benefit of a cytokine therapy may be due to effects on the malignant clone and/or on the residual normal hematopoiesis. Treatment with recombinant interferon-alfa (rIFN-a) in patients with hairy cell leukemia is an established therapeutic option. The administration of recombinant cytokines seems to be of potential benefit in some other malignant conditions (rIFN-a in CML, recombinant colony stimulating factors [rCSFs] in MDS or in combination with chemotherapy in AML and advanced MDS). The broad spectrum of activity of cytokines, the detection of novel biomolecules, and the expanding insight into disturbed regulatory mechanisms within a malignant clone suggest that the number of clinical applications for recombinant cytokines will further grow.
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PMID:[Status of recombinant cytokines in treatment of leukemic diseases]. 194 48

Transient neonatal myeloproliferative disorders (TMD's) indistinguishable from acute leukaemia by clinical and morphological criteria have been described in neonates with Down's syndrome. To analyse its clinical significance, 10 infants under 1 year of age presenting with Down's syndrome and the morphological picture of acute myelogenous leukaemia were reviewed. 3 of these children had true AML leading to death after 2, 8 and 11 months. In the other 7 children the diagnosis TMD was suggested as spontaneous or in one case interferon-induced remission occurred within 4 to 25 weeks after diagnosis. The interferon-treated patient died of SIDS at the age of 11 months. Another one of the TMD children developed fatal erythroleukaemia at the age of 2 years. Regarding initial clinical and haematological parameters, TMD was indistinguishable from true congenital leukaemie. In all patients classification according to the FAB criteria was difficult, as mainly undifferentiated or poorly differentiated myeloid blasts were seen, sometimes with erythro- or megakaryocytic features. Because of the difficulties in the differential diagnosis of TMD and true AML it is recommended to delay specific cytostatic therapy in neonates with Down's syndrome, until definite progression of the leukaemic process is observed or cytogenetic analyses suggesting true AML are available.
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PMID:[Transient myeloproliferation and acute myeloid leukemia in infants with Down's syndrome]. 214 25

We report on the fragile site expression in lymphocytes from 16 Down syndrome (DS) men aged 24 to 52 years. Among rare fragile sites, 16q22 has been reported to be induced or enhanced by alpha-interferon. Since DS cells have three copies of the receptor for alpha-interferon, we hypothesized a possible enhancement of 16q22 expression. This fragile site has also been related to a specific rearrangement in M4 acute nonlymphocytic leukemia. In view of the high incidence of acute leukemia in DS subjects, we studied the expression of 16q22 in lymphocyte cultures treated with 5-bromodeoxyuridine or alpha-interferon. We also studied whether the repair deficiency of DS cells could affect the expression of aphidicolin-induced fragile sites. The level of chromosomal aberrations was compared with that found in aphidicolin-treated cultures from 12 normal subjects of the same age. We found neither spontaneous or BrdU-induced fragility at 16q22 nor induction by alpha-interferon. Chromosomal breakage rate was increased in alpha-interferon-treated cultures in comparison with control cultures of the same subjects. Aphidicolin-induced fragile sites expression in DS patients did not differ significantly from that found in the lymphocyte cultures from control subjects.
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PMID:Chromosome fragile sites in Down syndrome patients. 214 45

The aim of differentiation therapy is to induce a maturation of the leukemic clone. Various approaches have been used: suppression of proliferation by low dose Ara-C in acute myeloid leukemia (AML); enhancement of differentiation by retinoic acid derivatives in acute promyelocytic leukemia (APL) or by differentiation-inducing factors; modulation of cell metabolism by breaking an autocrine loop in hairy cell leukemia (HCL). In all cases the treatment is given continuously at small doses over a long period of time. The very significant clinical results which have been obtained mainly in APL with all-trans retinoic acid and in HCL with alpha-interferon are briefly discussed.
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PMID:Differentiating agents in the treatment of leukemia. 220 23

In vitro and in vivo studies were conducted to obtain basic information on the activity of gamma interferon (IFN-gamma) in acute myelogenous leukemia (AML). In a selected case of AML, recombinant IFN-gamma, but not IFN-alpha, induced differentiation of primary leukemic blasts in vitro. Similarly, IFN-gamma inhibited leukemic colony formation in vitro. This contrasted with IFN-alpha which was inactive. In one case of AML (M2), partially purified IFN-gamma given intravenously caused a shift of the WBC profile from immature blasts to maturing myeloid cells and neutrophil granulocytes. Intravenous IFN-gamma treatment of another patient who had AML as a second malignancy resulted in a complete hematologic remission, normalization of marrow granulocyte-macrophage colony-forming cell in vitro growth, and conversion of marrow cytogenetics from 95% hyperdiploid clone with complex abnormalities into 100% diploid. The results indicate a potential use of IFN-gamma in the treatment of selected patients with AML and the possibility of in vitro pretreatment evaluation of these patients' leukemic response to IFNs.
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PMID:Hematologic response of four patients with smoldering acute myelogenous leukemia to partially pure gamma interferon. 244 29


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