Clinical

High-dose enzyme therapy speeds response of type 1 Gaucher disease

Last Updated: 2006-08-23 18:49:22 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Low-dose enzyme replacement therapy resolves the hematologic and visceral manifestations of type 1 Gaucher disease, but high-dose therapy leads to a more rapid response and may be more appropriate for patients with severe bone marrow involvement, a team of Dutch and German investigators report.

In patients with type 1 Gaucher disease, deficiency of the lysosomal enzyme glucocerebrosidase causes glucocerebroside to accumulate in spleen, liver and bone marrow. Enzyme replacement therapy, either with mannose-terminated enzyme from placental tissue (alglucerase) or recombinant enzyme (imiglucerase), is effective.

However, it is quite expensive and the most effective dosing regimen has not been determined. The authors estimate that a low-dose regimen would cost $70,000 per patient per year versus $380,000 for a high-dose course of treatment.

To address this issue, Dr. Carla E. M. Hollak, from the University of Amsterdam, and colleagues conducted a retrospective review of 49 adult patients with type 1 Gaucher disease treated at the Academic Medical Center in Amsterdam and 57 treated at Heinrich-Heine University in Duesseldorf, Germany between 1991 and 2002.

In Amsterdam, the median dose of enzyme replacement therapy was 15 to 30 U/kg/4 weeks, and in Duesseldorf, the median dose was 80 U/kg/r weeks. Median duration of treatment was 9 years and 7 years, respectively.

According to the report in the August 1 issue Blood, improvements in hemoglobin, platelet count and liver and spleen volume were not dose-dependent.

"Of all disease parameters, bone disease is the most difficult to evaluate," Dr. Hollak and her associates note. However, they add, "Improvement in bone marrow burden, an MRI-based scoring system of bone marrow involvement, shows a strong trend toward a better response to higher doses, particularly in patients with more extensive bone marrow disease in whom the difference is statistically significant."

Thus, they conclude that the initial dose should not be based on the extent of organomegaly and cytopenia. On the other hand, severe bone marrow involvement with its risk for bone complications may justify a higher initial dose.

Dr. Hollak's team recommends that "dosing regimen should be made individually and on the basis of a complete disease profile, including proper assessment of bone marrow involvement in addition to hematological, visceral, and biochemical parameters."

Blood 2006;108:830-835.