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  • L-asparaginase  (2)
  • Springer  (2)
  • The American Society for Biochemistry and Molecular Biology (ASBMB)
  • 1
    ISSN: 1432-1076
    Keywords: Acute lymphoblastic leukemia ; L-asparaginase ; Lipid metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract L-asparaginase is an effective antileukaemic drug and a potent inhibitor of hepatic protein synthesis. Its effect on lipid metabolism was studied in two cohorts of children with ALL, one of whom received L-asparaginase concomitantly with three other drugs (protocol BFM 79). In the second protocol (BFM 83) administration of L-asparaginase was arranged to follow the other three drugs in time sequence. The two major findings of this study were elevated serum levels of total cholesterol and a strong increase in serum triglycerides. The former change was due to an increase in α-cholesterol and could not be attributed to L-asparaginase because it was also found following protocol BFM 83 before the administration of the drug. Elevations of total triglycerides were due to high levels of exogenous chylomicron bound triglycerides and were limited in occurrence almost exclusively to the period of L-asparaginase monotherapy. Hypothyroidism was excluded as a possible pathogenetic mechanism. These changes in lipid metabolism induced by L-asparaginase during intensive remission induction chemotherapy are fully reversible.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1076
    Keywords: Acute lymphoblastic leukemia ; Hypothyroidism ; L-asparaginase ; Thyroxine binding globulin ; Thyroid hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently it has been observed that L-asparaginase causes transient thyroxine binding globulin (TBG) deficiency in adults. In the present study we investigated the influence of L-asparaginase on the pituitary-thyroid axis and on the synthesis of TBG. 14 children with acute lymphoblastic leukemia were treated with a combination of L-asparaginase, vincristine, prednisone and daunomycin for remission induction. Thyroid function was monitored by measuring total T4, free T4, total T3, TSH and TBG with specific radioimmunoassays before, during and after treatment. Within 3 weeks of L-asparaginase therapy total T4 fell significantly from 10.7±1.6 to 2.9±1.8 μg/100 ml, free T4 from 1.77±0.4 to 0.94±0.35 ng/100 ml, total T3 from 0.99±0.23 to 0.35±0.2 ng/ml and TBG from 29.4±3.6 to 8.0±3.8 μg/ml. Basal TSH values tinuation of L-asparaginase, but following further treatment with other antileukemic agents, all values became normal within 2–4 weeks. In 6 patients with hypothyroid free T4 values TRH induced TSH release was totally blocked during L-asparaginase therapy. Our data clearly demonstrated that L-asparaginase caused a transient TBG deficiency. Total T4 and T3 were in the hypothyroid range because of low TBG concentrations. In addition to TBG deficiency transient, secondary hypothyroidism occurred in approximately 40–50% of all patients treated with L-asparaginase. These alterations were most likely caused by drug induced inhibition of protein synthesis. Under certain circumstances thyroid hormone replacement might be life-saving in severely ill patients suffering from transient, drug induced hypothyroidism.
    Type of Medium: Electronic Resource
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