Submitted March 17, 2006
Accepted March 17, 2006
Low-dose therapy trumps high-dose therapy again in the
treatment of Gaucher disease
Ari Zimran, Deborah Elstein, and Ernest Beutler*
Gaucher Clinic and Department of Medicine, Shaare Zedek Medical Center, Jerusalem, Israel
The Scripps Research Institute, La Jolla, CA, USA
* Corresponding author; email: beutler{at}scripps.edu.
The paper by De Fost et al. in the current issue of Blood
contains important data with regard to dose-sensitivity in
the treatment of Gaucher disease, but the title is
misleading. It implies that high-dose enzyme replacement
therapy may be superior to low-dose enzyme replacement
therapy. However, it is apparent that "superiority" in
response is limited to two surrogate markers, serum
chitotriosidase and marrow fat content as measured by MRI.
Importantly, the improvement in hematologic findings,
organomegaly, and frequency of skeletal crises, is
equivalent in low-dose and high dose therapy. Contrary to
what De Fost et al. imply, neither serum chitotriosidase
nor marrow fat are clearly related to disease severity,
and we aver that the response of surrogates is of little
importance selecting a program of treatment for a patient.
Given the very high cost of enzyme replacement therapy,
the study by De Fost et al. is another compelling reason
for physicians not to use high-dose therapy in the
treatment of Gaucher disease.
