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

dictor of OS (p=0.004). High dose therapy was not able to overcome
this poor prognostic effect of HD. FC may be a useful tool in defining
high risk patients.
Figure 1. Survival functions.
1093
DYSPLASIA SCORING SYSTEM FOR ASSESSMENT OF MYELODYSPLASIA IN MDS
AND SECONDARY LEUKAEMIA, AND ITS APPLICATION TO THE WHO CLASSIFICATION
V. Andrieu, 1 E. Duchayne, 2 M.J. Grange, 1 M. Guesnu, 3 M. Imbert, 4
F. Picard3 1 CHU Bichat-claude Bernard, PARIS, France; 2 CHU Purpan, TOULOUSE,
France; 3 CHU Cochin, PARIS, France; 4 CHU H Mondor, CRETEIL, France
The World Health Organization (WHO) classification extends to the
morphologic criteria of the FAB proposal, the recognition of the impact
of multilineage dysplasia in myelodysplastic syndromes (MDS). Besides
the usual epidemiological, clinical and biological data, register of the
Groupe Français des Myélodysplasies (GFM) includes morphologic criteria.
A structured image case of representative pictures of haematopoietic
cell lineages is recorded for each patient by the diagnostic centre, following
a standardized protocol. A multicentric analysis of cytologic features
of blood and bone marrow cells is then performed on line, at least
by 3 other observers. Megakaryocytic, erythroid, and myeloid dysplasia
is classified into seven, four, and ten categories respectively, and a
score is associated for each morphologic dysplasia criteria. Morphologic
dysplasia in blood and bone marrow cells is also analysed according
to the WHO criteria. This structured cytomorphological examination of
recorded pictures has been performed in 120 MDS patients, from 20
French centres of the GFM. This dysplasia scoring system allowed a
more structured and reproducible approach for the precise definition
and quantification of dysplastic bone marrow features. Thus, it improved
interobserver agreement for the WHO classification of MDS patients,
particularly in the subgroups with multilineage dysplasia. Our study,
using an on line application, confirmed the significance of multilineage
dysplasia correlation with high-grade MDS and pointed out links of
some dysplasia criteria with WHO classification subgroups or with
blood or cytogenetic abnormalities. This suggests that a standardized
dysplasia scoring system could improve diagnostic classification of MDS
patients and then could help to define standards for evaluations, patients'
selection and for the use of targeted drugs in the various subgroups of
MDS.
1094
FLUDARABINE, CYCLOPHOSPHAMIDE AND RITUXIMAB UP TO FOUR COURSES AS FIRST
LINE TREATMENT FOR INDOLENT NON-HODGKIN LYMPHOMAS
J.F. Falantes, E. Ríos Herranz, A. Marín Niebla, M.L. Martino Galiana,
R. Parody, J.M. Blas Orlando
Hospital Universitario Virgen del Rocío, SEVILLE, Spain
Aims. Evaluate response rate and toxicity associated to fludarabine,
cyclophsphamide and rituximab (FCR) up to four courses as first line
treatment for indolent Non-Hodgkin Lymphomas (NHL). Methods. This
Phase II study evaluated patients (pts) with histopathologic diagnosis of
indolent NHL with clinical stages III and IV, treated with FCR combina-
12 th Congress of the European Hematology Association
tion up to four courses. Fourty seven pts were included (37 pts with Follicular
lymphoma, 6 pts with Marginal Zone Lymphoma and 4 pts with
Lymphoplasmacytic Lymphoma/Waldenström). Median age was 51.6
years (34-78). Treatment schedule: rituximab 375 mg/m 2 day 1, and fludarabine
25 mg/m 2 cyclophosphamide 300 mg/m 2 days 2-4. All pts
received prophylaxis with cotrimoxazole, acyclovir and fluconazole. G-
CSF (5 g/kg/day) was added if absolute neutrophil count 2, with 6 episodes of febrile neutropenia.
Other toxicities: Transient elevation of liver function test (>2.5-
5.0 ULN) and transient grade 3 gastrointestinal toxicity (vomiting that
required iv fluids). 2 pts experienced zoster reactivation. 1 pt developed
grade 3 severe skin reaction after rituximab. Only 3 pts did not complete
proposed schema for intolerance to rituximab (infusion related reactions)
in some course. 2 pts maintain hematologic toxicity after achieved CR.
Conclusions. FCR schema achieves significant high ORR (CR + PR: 94.8%)
as first line treatment for indolent NHL stages III and IV. This results support
possible role for maintenance with rituximab in this pts as intent to
prolong responses. This combination up to four courses is relatively well
tolerated, thoug significant citopenias were observed, with subsequent
delay in treatment courses. Neutropenia was most common toxicity,
but it did not result into high rate of infectious complications compared
to other schedules that include six corses of this combination with similar
ORR.
1095
METHYLATION STATUS OF THE WNT ANTAGONIST DICKKOPF-1 GENE IN ACUTE
LEUKEMIAS
F. Atalar, 1 O. Hatirnaz, 2 M. Sayitoglu, 1 Y. Erbilgin, 1 U. Ozbek2 1 Istanbul University, DETAE Genetics Dept, ISTANBUL, Turkey; 2 Istanbul
University,DETAE Genetics Dept, ISTANBUL, Turkey
Background. Wnt proteins regulate development and homeostasis by
binding to membrane Frizzled-LRP5/6 receptors. Wnt signaling is
through a canonical pathway involving cytosolic β-catenin stabilization,
nuclear translocation and gene regulation, acting as a co-activator of Tcell
factor (TCF) proteins, and noncanonical pathways that activate Rho,
Rac, JNK and PKC, or modulate Ca 2+ levels. DICKKOPF-1 (DKK-1)
encodes a secreted Wnt antagonist that binds to LRP5/6 and leads to
inhibition of the canonical pathway. Aim. to study the role of methylation
of DICKKOPF-1 (DKK-1) in acute leukemia. Methods. DKK-1, Wnt
antagonist, was studied in untreated 35 AML patient and 78 ALL patient
bone marrow and/or blood samples and normal hematopoietic cells by
bisulfite modification of DNA, followed by the use of the methylationspecific
PCR assay (MSP). This assay was further validated in vitro by SSI
methylase. Results. At diagnosis, Dkk-1 was methylated in 44.8% (30/78)
of acute lymphoblastic leukemia. Interestingly, in acute myeloid
leukemia (AML) Dkk-1 (an antogonist of WNT5A) gene methylation
status was determined to be 52% (16/35). Conclusion. Here, we show for
the first time that extracellular Wnt inhibitor, the Dkk-1 gene, is transcriptionally
silenced by CpG island promoter hypermethylation in acute
leukemias.
1096
EFFECTS OF HUMAN BONE MARROW STROMAL CELL LINE ON THE PROLIFERATION,
DIFFERENTIATION AND APOPTOSIS OF HL-60 CELLS
R. Liang
Xijing hospital, XI’AN, China
Introduction. Rapid advances have been made in elucidating the molecular
mechanism of etiology and pathogenesis of leukemia, while less
attention has been directed toward examining the role of the hematopoietic
microenvironment(HM) in the initiation and progression of
leukemia. As we know, HM can regulate hematopoiesis through interactions
with progenitor cells, hematopoietic cytokines and the biosynthetic
products of stromal and other cells. Acute myeloid leukemia(AML)
initiates and progresses in the HM. Encounters between the HM and
leukemic cells may affect the apoptosis, differentiation and proliferation
of leukemia cell. The bone marrow microencironment is presumed to
play an essentially regulatory role in determining the fate of leukemic
cells.Objective To investigate the effects of human bone marrow fibrob-
haematologica/the hematology journal | 2007; 92(s1) | 403