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

12 th Congress of the European Hematology Association
this report, we identified HPR-induced reactive oxygen species (ROS)
generation as the key mediator of cell cycle arrest and apoptosis of malignant
T cells. HPR treatment of HTLV-I negative malignant T cells was
associated with a rapid and progressive ROS accumulation. Pre-treatment
with the anti-oxidants vitamin C and dithiothreitol inhibited ROS
generation, prevented HPR-induced ceramide accumulation, cell cycle
arrest, cytochrome c release, caspase-activation, and apoptosis. Therefore,
anti-oxidants protected malignant T cells from HPR-induced
growth inhibition. The expression of the HTLV-I oncoprotein Tax abrogated
HPR-induced ROS accumulation in HTLV-I infected cells, which
explains their lower sensitivity to HPR. Summary and Conclusions. Defining
the mechanism of free radical induction by HPR may support a
potential therapeutic role for this synthetic retinoid in ATL and HTLV-
I-negative T-cell lymphomas.
0734
ENZYME REPLACEMENT THERAPY DOSE-RESPONSE RELATIONSHIPS IN PATIENTS WITH
TYPE 1 GAUCHER DISEASE
S. vom Dahl, 1 G.A. Grabowski, 2 J. Charrow, 3 C.E.M. Hollak, 4
K. Kacena, 5 P.K. Mistry, 6 L. Zhang, 5 A. Zimran7 1 St. Franziskus-Hospital, COLOGNE, Germany; 2 Cincinatti Children's Hospital,
CINCINATTI, USA; 3 Childrens Memorial Hospital, CHICAGO, USA;
4 Amsterdam Medical Center, AMSTERDAM, Netherlands; 5 Genzyme Corp.,
CAMBRIDGE, USA; 6 Yale University School of Medicine, NEW HAVEN,
USA; 7 Shaare Zedek Medical Center, JERUSALEM, Israel
Aims. To analyze if enzyme replacement therapy (ERT) with
imiglucerase demonstrates dose-response relationships in patients with
type 1 Gaucher disease (GD) within the range of doses used in routine
clinical practice and across disease parameters. Methods. The analysis
included all patients with type 1 GD enrolled in the ICGG Gaucher Registry,
diagnosed in 1991 or later, received ERT with imiglucerase, and had
an intact spleen. ERT dose was defined as the average dose over the first
3 years of treatment. Propensity score matching was used to control for
differences in baseline disease severity between ERT dose groups categorized
as 15U/kg (5″,