Treatment of Acute Lymphoblastic Leukemia in Children with the BFM Protocol: A Cooperative Study and Analysis of Prognostic Factors

Maurus, R; Boilletot, A; Otten, Jacques; Philippe, N; Benoît, Yves; Béhar, C; Daele, M Casteels-Van; Chantraine, Jean‐Marie; Delbeke, M J; Gyselinck, J; Hainaut, H; Lutz, Pierre G.; Plouvier, Emmanuel; Robert, Annie; Sauveur, E.; Solbu, G.; Souillet, G; Suciu, Stefan

doi:10.1007/978-3-642-71213-5_82

Cited by 6 publications

(2 citation statements)

References 2 publications

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“…Fifty-seven childr en (23 girls and 34 boys) with acute lymphoblastic leukemia from the pediatric hematology departments of Lille , Nantes, and Poitiers University Hospitals were treated between August 1989 and January 1993 according to the Children' s Leukemia Cooperative Group protocol (11). The mean age of the patients was 6 y (range, 1 to 16 y; median, 5 y).…”

Section: Methodsmentioning

confidence: 99%

Changes of Cerebral Biopterin and Biogenic Amine Metabolism in Leukemic Children Receiving 5 g/m2 Intravenous Methotrexate

Millot

Dhondt²,

Mazingue

et al. 1995

Pediatr Res

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Acute or subacute neurologic disorders can be observed in patients receiving high-dose methotrexate therapy for lymphoblastic leukemia or malignant tumor. Impairment of biopterin metabolism leading to decreased availability of monoamine neurotransmitters has been suggest ed to explain methot rexate neurotoxicity. To investigate such a mechanism, we have measured prospectively by HPLC the concentra tions of total biopter in, homovanillic acid, and 5-hydroxyindo lacetic acid in cerebrospinal fluid of 57 children with acute lymphoblastic leukemia. A sequential analysis of cerebrospinal fluid was performed for each patient: cerebrospina l fluid samples were obtai ned before therapy and after each of the four high-dose methotrexate infusions during the CNS proph ylaxis phase. A significant increase of total biopterin conce ntrations in cerebrospinal fluid was observed after high-dose methotrexate therapy com pared with the pretreat ment values. No cumulative effect was noted. In contrast, no signifiChildren with leukemia or malignant tumor receiving intrathecal or i.v. MTX may develop acute or subacute encephalopathy (1, 2), suggesting a direct effect of the drug on the brain metabolism. The hypothesis of impaired neurotransmitter synthesis has been proposed to explain the occurrence of these abnormalities (3). The biogenic ami ne neurotransmitters are produced in the brain at a rate-limiting hydro xylation from precursor amino acids. Tetrahydrobiopt erin is the essential cofactor of this hydroxylation step. DHPR maintain s adequate leve ls of tetrahydrobiopterin, and the inherited deficiency of DHPR leads to impaired neurotransmitter amine synthesis and severe neurologic disease (4). It has been suggest ed that MTX,

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Section: Methodsmentioning

confidence: 99%

Changes of Cerebral Biopterin and Biogenic Amine Metabolism in Leukemic Children Receiving 5 g/m2 Intravenous Methotrexate

Millot

Dhondt²,

Mazingue

et al. 1995

Pediatr Res

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“…Glucocorticoid hormones (GC) modulate gene transcription in a tissue-specific manner [1]. In tissues of lymphatic origin they are capable of mediating the induction of apoptosis and GC-hormones are therefore included in most protocols for treatment of leukemia and lymphoma [2,3]. The intracellular signal transduction of the hormone is mediated by the glucocorticoid receptor (GR), a protein capable of interacting with the ligand as well as with the steroid responsive elements in the DNA [4].…”

Section: Introductionmentioning

confidence: 99%

High levels of non-activated receptors in glucocorticoid-sensitive S49wt mouse lymphoma cells incubated with dexamethasone

Berg

Smets

Hutchison

et al. 1994

The Journal of Steroid Biochemistry and Molecular Biology

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Upon agonist binding the heteromeric glucocorticoid receptor complex undergoes a conformational change (receptor activation). This event involves the dissociation of a dimer of 90 kDa heat shock proteins. Whereas receptor activation in cytosolic assays is both rapid and irreversible, less is known about the receptor activation and translocation in intact cells during challenge with an agonist. In this paper we report on the receptor status of glucocorticoid-sensitive murine S49 lymphoma cells during dexamethasone exposure. By three different assays, ligand (re)binding, nuclear translocation and hsp90 co-immunoprecipitation, it was found that the majority of the glucocorticoid receptor protein was in a non-activated conformation. Furthermore, prolonged exposure to dexamethasone did not result in increased levels of activated receptors. By assessing receptor activation in situ we found that physiological temperature was less effective in dissociating hsp90 compared to room temperature. These findings indicate that the physiological temperature negatively controls receptor activation, probably due to a thermolabile interaction between the hormone and its cognate receptor.

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The Children Leukemia Group

Otten¹,

Philippe

Suciu

et al. 2002

European Journal of Cancer

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Treatment of Acute Lymphoblastic Leukemia in Children with the BFM Protocol: A Cooperative Study and Analysis of Prognostic Factors

Cited by 6 publications

References 2 publications

Changes of Cerebral Biopterin and Biogenic Amine Metabolism in Leukemic Children Receiving 5 g/m2 Intravenous Methotrexate

Changes of Cerebral Biopterin and Biogenic Amine Metabolism in Leukemic Children Receiving 5 g/m2 Intravenous Methotrexate

High levels of non-activated receptors in glucocorticoid-sensitive S49wt mouse lymphoma cells incubated with dexamethasone

The Children Leukemia Group

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