12th Congress of the European Hematology ... - Haematologica

modulated after 24 h (37 up- and 59 down-regulated), most of which
involved in cell cycle regulation. Changes in cyclin D1 and D3, cyclin E
and cdc 25A were also validated at the protein level. Conclusions. The
strong growth-inhibitory and pro-apoptotic activity induced in vitro by
PD0325901 suggests that MEK may be an appropriate therapeutic target
in hematological malignancies, particularly in myeloid leukemias.
0748
LONG TERM EFFICACY AND SAFETY OF MIGLUSTAT THERAPY IN TYPE 1 GAUCHER
DISEASE
M. Giraldo, 1 P. Latre, 2 A. Acedo, 3 D. Alonso, 4 A. Barez, 5 A. Martín, 6
R. Franco, 7 A. Fernández-Villamor, 8 M. Pocovi, 9 SGGD Spanish Group
on Gaucher Disease2 1 Miguel Servet University Hospital, ZARAGOZA; 2 FEETEG, ZARAGOZA;
3 Hospital Vega Baja, ALICANTE; 4 Hospital U Virgen del Rocío, SEVILLA;
5 Hospital Ntra Sra Sonsoles, AVILA; 6 Hospital Ntra Sra de la Concha, ZAMO-
RA; 7 Hospital U Punta Europa, CÁDIZ; 8 Complejo hospitalario San Millan, LA
RIOJA; 9 Universidad, ZARAGOZA, Spain
Background and Objective. Gaucher disease (GD) is the most common
lysosomal storage disease. Miglustat ZAVESCA, is a synthetic iminosugar
which acts as an inhibitor of the enzyme glucosylceramide synthase
(SRT). This therapy offers an alternative approach for GD based on the
indirect effect reducing the burden of glycolipids delivered to the
macrophage system after phagocytosis of formed blood cells. We present
the results after more than 24 months on an everyday clinical use of
oral therapy in type 1 GD patients. Design and Methods. The Spanish
group on GD design a structured project named with the acronymus
ZAGAL. It includes a set of recommendations in a structured protocol
for collecting safety, efficacy and QoL data at 6, 12, 24 months and
beyond. The project’s aim is to guarantee the safe and proper use of
Zavesca in an everyday clinical use. Baseline assessment: complete clinical,
analytical and imaging evaluation, detailed neurological exam and
superficial electroneurogram in sural and peroneal nerve. Cognitive test
and memory impairment screen for dementia assessment were used. A
free lactose and low carbohydrate diet (FLLCD) were recommended and
applied in first weeks on therapy. Results. 41 GD patients (females
56.1%). mean age 46.4.y (range: 21-74), SSI 5.8 (range: 2-9), spleen
removal 9.5%, chitotriosidase activity 3,286 nM/mL.h (range 468-
10,553), CCL18/PARC 533 (range 102-1,219). Ten patients was naïve to
SRT, mean age: 46.7y. Thirty one patients were included on SRT once
stabilising their disease with Imiglucerase during a mean of 3.8 y (range:
2-11), dose 30-60 U/kg, mean age 39.2 y; mainly heterozygous for
N370S. In February 2007 15 patients had completed 24 months on SRT,
21 patients 12 months and 10 naïve patients/13 switch 6 months.
Response: all patients with anaemia improved haemoglobin concentration
(mean 0.8 g/dL). Platelet count improved in patients with lowest values
and it was maintained in patients with counts in normal limits. Chitotriosidase
activity was maintained in switched patients and slightly
decreased in naïve patients. The response was observed at 6 months on
therapy and it is maintained after 24 months on therapy. In 7 naïve
patients bone marrow MRI improvement was documented. No new
symptoms were developed, three patient discontinued SRT due to poor
compliance. Gastrointestinal disturbance appeared sporadically in five
patients and became normal when they followed the FLLCD. One
patient had a significant weight loss (