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Enzyme therapy in Gaucher disease type 1: dosage efficacy and adverse
effects in 33 patients treated for 6 to 24 months
GM Pastores, AR Sibille and GA Grabowski
Division of Medical and Molecular Genetics, Mount Sinai School of Medicine,
New York, NY.
Gaucher disease is the most frequent lysosomal storage disease and the most
prevalent genetic disease among the Ashkenazi Jews (q approximately 0.047).
The disease results from inherited defects of acid beta-glucosidase and the
accumulation of the substrate, glucosylceramide, in cells of
monocyte/macrophage origin. The therapeutic response to macrophage-targeted
(alpha-mannosyl-terminated) alglucerase (Ceredase, at 60 to 15 IU/kg every
2 weeks) was analyzed in 33 patients (age range, 2 to 63 years; 15
splenectomized) with extensive Gaucher disease over periods of 6 to 24
months. The efficacy of several different doses and dosage reductions was
evaluated. In patients with anemia (n = 30) and/or thrombocytopenia (n =
19), hemoglobin levels and platelet counts increased by 0% to 178% and 15%
to 155%, respectively, within 3 to 12 months. In patients with splenomegaly
(n = 17) and/or hepatomegaly (n = 28), liver and spleen volumes decreased
in 6 months from 7% to 64% and 8% to 84% by 12 months, respectively.
Hematologic and visceral improvements were noted at any doses between 60
and 15 IU/kg every 2 weeks. Furthermore, these positive initial therapeutic
responses were persistent throughout therapy, with doses reduced by 50%.
Pulmonary Gaucher disease did not improve clinically in 3 patients.
Unrelated cirrhotic (n = 2), cholestatic (n = 1), or renal disease (n = 1)
did not influence the rate of patient improvement. Two of five patients who
developed serum antibodies against alglucerase during the first 6 to 12
months of therapy had mild antibody reactions. This study shows similar
regression of clinical Gaucher disease manifestations with enzyme therapy,
using doses between 30 and 60 IU/kg every 2 weeks. Therapeutic efficacy was
not diminished after 50% to 75% dose reductions or in the presence of
anti-enzyme antibodies.
Volume 82,
Issue 2,
pp. 408-416,
07/15/1993
Copyright © 1993 by The American Society of Hematology
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