TREATMENT OF GAUCHER’S DISEASE IN GREEK ADULT PATIENTS: INITIAL LONG TERM ANALYSIS OF A COLLABORATIVE STUDY OF ENZYME REPLACEMENT THERAPY
Th. Marinakis, C. Repa, P. Karkalousos, P. Tsaftaridis, A. Symeonidis, A. Kammas, H. Michelakakis
Enzyme replacement therapy (ERT) in Type 1 Gaucher’s disease (GD) with enzyme intravenous infusions (alglucerase and imiglucerase) has been proved to be effective in ameliorating or reversing many disease manifestations including hematologic, visceral and skeletal abnormalities and led to improved general health and quality of life. An alternative approach involving the reduction of biosynthesis of glycosylceramide with oral N-butyldeoxynojirmycin (miglustat) has been used the last years for patients unable or unwilling to receive enzyme therapy.
This study presents our experience since April 1995 with 23 Greek adult patients (12 males, 11 females) aged 19-65 (mean age 33, median age 28) years with type 1 GD in therapy. Two patients (1male/1female) -unwilling to this therapy- have recently started receiving miglustat. These were the patients we believe they required ERT. Before initiating the enzyme therapy our patients showed: anaemia (Hb<11,5g/dl) 16/23, thrombocytopenia (PLT<60.000/mm3) 12/23. They all had hepatomegaly, 8/18 had massive splenomegaly (five patients splenectomized) and 8/23 bone disease. The diagnosis was confirmed in all patients by assaying glucocerebrosidase activity after a bone marrow biopsy (or a liver biopsy), while a DNA analysis was performed. All patients presented with elevated acid phosphatase and chitotriosidase activity values.
Alglucerase and imiglucerase injections were intravenous administered at a dose of 15-60 IU/Kg (depending on symptoms) once every 2 weeks (two patients every 4 weeks) for the first 6-12 months (induction period) followed thereafter by a monthly dose reduction (maintenance period), if this was possible.
After induction therapy patients increased their weight (2-10Kg) They also improved significantly their haematological parameters-as early as four to six months on therapy-especially in the hemoglobin (Hb levels increased 2 g/dl, range 0,9-3 g/dl), while most of them reached normal platelet counts. Liver and spleen sizes were objectively decreased (mean volume 18% and 30% respectively within the first year and 35% and 40% at the end of five years). Bone disease was halted and mean bone density improved. Acid phosphatase and chitotriosidase activity values decreased with treatment in all patients. Quality of life was improved significantly in all patients and their therapy was well tolerated. Our patients have completed 6months–9 years of treatment and most continue to date (except one patient).
ERT with imiglucerase can be effective in the reversal of cytopenias and organomegaly in patients with GD improving also quality of life. Further studies are necessary to compare therapeutic responses on varying doses of enzyme during induction and maintenance periods among these patients.
Tελευταία ενημέρωση: Δευτέρα Σεπτεμβρίου 07, 2009