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

12 th Congress of the European Hematology Association
anemia), therapeutic treatments (e.g. transplantations) and supportive
care (e.g. transfusion support) will be requested in the future. Since most
of the MDS patients are not eligible for transplantation it can be assumed
that the economic burden of MDS is determined predominantly by anemia
and transfusions. Aims. To describe the economic burden of transfusion
and anemia in MDS on the basis of published literature. To make
a first estimate of the economic impact for Germany. Methods. Literature
search via PUBMED was systematically conducted (covering 1/96 to
12/06) using the search terms: Myelodysplastic Syndrome AND Transfusion
AND Cost and cost analysis OR cost of illness OR health care
costs OR epidemiology; anemia AND cancer AND cost OR transfusion.
Further desk-top researches were conducted to evaluate the economic
burden of transfusion-dependency of MDS patients from the German
transfusion medicine’s perspective. Results. Three MDS cost-analyses
focus on transfusion costs and present direct costs from the payers’ perspective.
Regarding anemia in cancer patients 4 cost-of-illness analyses,
4 cost-effectiveness-analyses, 3 cost-minimisation analyses and 4 other
cost analyses were identified. Most studies analyse the US-American situation
from the payers’ perspective. Prevalence of MDS in Germany is
estimated to range between 7,300 and 10,500 patients. Assuming a need
of 24 erythrocytes per transfusion dependent MDS patient per year in
average, MDS transfusions add up to 2 to 3 per cent of whole erythrocyte
production in Germany in 2004. Depending on the current unit
price of erythrocytes and the numbers of transfusion dependent MDS
patients, the total costs of transfusion vary between 8 and 23.5 million
Euro per year. The number of transfusion dependent MDS patients will
grow by approximately 1,760 up to approx. 7,200 patients in Germany
in 2010 resulting in transfusion costs between 15 and 30 million Euro.
Summary and Conclusions. There is a lack of information on the economic
burden of MDS. To evaluate the economic consequences of innovative
therapeutics in MDS it is important to provide information of
resource consumption and the respective costs on the basis of real life
data. It is important to present the results by disease severity and treatment
options. The treatment of transfusion dependent MDS is of special
public health interest. Blood is an increasingly scarce and expensive
resource and unnecessary transfusions may cause a shortage of blood
products for patients in real need. Therefore the value of blood conserving
strategies should be evaluated from a broader perspective - the societal
perspective.
0842
PHARMACOGENOMIC APPROACH OF SICKLE CELL DISEASE TREATMENT: GLOBAL
ANALYSIS OF HYDROXYUREA EFFECT ON HUMAN ENDOTHELIAL CELLS
TRANSCRIPTOME
S. Laurance, 1 A. Benecke, 2 E. Verger, 1 R. Krishnamoorthy, 1 J. Elion, 1
C. Lapoumeroulie1 1 UMR INSERM U763/Université Paris7, PARIS; 2 Institut des Hautes Etudes
Scientifiques, BURES SUR YVETTES, France
Background. The clinical hallmarks of sickle cell disease (SCD) are
recurring painful vaso-occlusive episodes, chronic anaemia and multiple
organ damages. Although the polymerisation of Haemoglobin S (HbS)
is the base of the pathophysiology, the vascular endothelium seems to
play an essential role in vascular occlusion. Hydroxyurea (HU) is the
only drug with a measurable clinical benefit for SCD patients by reducing
the frequency of vaso-occlusive crisis. Initially, HU was administrated
to induce HbF expression but there is no link between the observed
clinical benefit and the expected increase of HbF expression. Due to the
crucial role of ECs in SCD, our laboratory investigates the effect of HU
therapy on ECs. Indeed, we have shown that HU affects the expression
of specific endothelial genes. These genes seem to be implicated in the
pathobiology since they encode for adhesion molecules (VCAM-1),
vaso-modulators (endothelin-1) and cytokines (Il-6, Il-8). Aims. We decided
to pursue analysis of HU effect on endothelial cells in the way to identify
HU targets genes and downstream pathways by establishment of
differential transcriptome profiling of human ECs (cells exposed to HU
vs unexposed). Methods. Our analysis was performed by a systematic
screening of HU target genes based on the use of a micro-array system
which allows to evalute the expression level of the whole human transcriptome
since the array contains probes for 29,198 identified genes. We
have analysed the effect of HU 24h treatment period on the transcriptome
profile of a human endothelial cell line derived from bone marrow
microcirculation (TrHBMEC). Results. The subtraction profile (HU vs
non-treated) identifies 2448 potential novel target genes. RQ-PCR experiments
were carried out to validate the method applied and these differentially
expressed HU target genes. Among them, thrombospondin-
1 (TSP-1), von Willebrand factor (vWF), PECAM-1, AXL mRNA levels
314 | haematologica/the hematology journal | 2007; 92(s1)
are decreased and interleukin-1 α and β mRNA are increased. All these
factors seem to be relevant for the pathobiology and endothelium functions.
In fact, TSP-1 and vWF are implicated in adherence and coagulation
events and high levels of these two proteins are detected in SCD
patients. PECAM-1 modulates vascular permeability and lymphocytes
extravasation, AXL is a new vascular system regulator and is implicated
in adhesion phenomenon. IL-1 α and β are pro-inflammatory
cytokines; their up-regulation by HU is paradoxical with the improved
clinical features. Experiments at the protein level are thus carried out to
validate the mRNA data. Conclusion. Presently, we find, by an exhaustive
transcriptome analysis, new relevant endothelial target genes of
HU, however some of our results seem to be inconsistent with clinical
benefits suggesting that SCD and its treatment are complex and require
more experiments. The same type of microarrays experiments has also
been carried out combining pro-inflammatory cytokines and hydroxyurea
treatment in a way to simulate SCD inflammatory context. A
global signaling pathway analysis of the data is performed to identify the
biological processes and the molecular pathways affected by HU. A better
understanding of HU molecular effects and downstream pathways
should lead to the emergence of improved and more targeted therapies.
0843
ANGIOGENESIS AND PERYCYTE MARKERS IN SEVERE HEMOPHILIACS WITH DIFFERENT
CLINICAL PHENOTYPES
A. Calleri, 1 L. Saronni, 2 E. Biguzzi, 3 F. Franchi, 3 P. Mancuso, 2
C. Rabascio, 2 V. Raia, 2 M.E. Mancuso, 3 E. Santagostino, 3 P. Antoniotti, 2
J. Quarna, 2 P.M. Mannucci, 3 F. Bertolini2 1 European Institut of Oncology, MILAN; 2 European Institute of Oncology,
MILAN; 3 Ospedale Maggiore di Milano, MILAN, Italy
Background. Haemophilia is an inherited hemorrhagic disorder, characterized
by spontaneous bleeding episodes. However, some severe
haemophilic patients exhibit a mild bleeding tendency. It is possible to
hypothesize that the vascular and perycyte component of haemostasis
can influence the capacity of repairing vascular damage in these individuals.
Aims. to investigate different surrogate markers of angiogenesis
and vasculogenesis in haemophilic patients. Methods. Two groups of
patients with severe haemophilia were enrolled: 11 mild bleeders (MB:
≥2 spontaneous bleeding episodes/year; concentrate use