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

12 th Congress of the European Hematology Association
ance of the original clone marked by t(7;16)(p15;p13) and developed a
new clone marked by 5q- along with +8 just before AML progression.
In conclusion, i) in our series karyotipic evolution occurred in ablout
31% of patients; ii) some non clonal defects, which presence was not
confirmed by FISH, simply signaled the instability of the dysplastic
clone; iii) some clonal defects, especially +8, del(7)(q31q35) and 17p-,
represented true steps in disease progression; iv) cytogenetic evolution
significantly predicted MDS/AML progression and when occurred in
patients of the IPSS good risk cytogenetic category completely changed
their outcome.
0225
T-CELL RECEPTOR VΒ CDR3 OLIGOCLONALITY FREQUENTLY OCCURS IN CHILDHOOD
REFRACTORY CYTOPENIA
A. de Vries, 1 M.M. van den Heuvel-Eibrink, 1 A.C.H. de Vries, 1
B. Verhaaf, 2 C.M. Niemeyer, 3 J. Stary, 4 K. Schmiegelow, 5
E.R. van Wering, 6 A. Beishuizen, 1 A.W. Langerak, 2
1 2 Erasmus MC Sophia Children's Hospital, ROTTERDAM, Netherlands; Erasmus
MC, Department of Immunology, ROTTERDAM, Netherlands; 3Univer sity of Freiburg, FREIBURG, Germany; Charles University, PRAGUE, Czech
Republic; 5National University Hospital, COPENHA; 6Dutch Childhood Oncology
Group, THE HAGUE, Netherlands
Background. Severe acquired aplastic anemia (SAA) and myelodysplastic
syndrome (MDS) are rare diseases in childhood. SAA is a bone marrow
failure syndrome charecterized by immune mediated destruction
of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder,
in which the hypoplastic variant is, in case of absence of a cytogenetic
clone, difficult to separate from SAA. Recently, studies provided
a molecular signature of autoimmunity in adult SAA, by showing oligoclonality
of TCR Vβ CDR3 region, which is refered to as TCR Vβ skewing.
We investigated the value of TCR Vβ repertoire analysis in pediatric
MDS-RC and (v)SAA patients. Methods. Peripheral blood and/or bone
marrow mononuclear samples of patients with (v)SAA (n=38), MDS-RC
(n=28) and 18 controls were analysed with Vβ heteroduplex analysis of
extracted RNA. Results.Skewing was found in 21/38 (55%) of the SAA
patients and in 17/28 (61%) of the RC patients. Seventeen patients with
clinical SAA showed no oligoclonality. A significant difference in TCR
skewing was found between the (v)SAA + MDS-RC patients as compared
to the controls (χ2 analysis, p=0.001), but not between MDS-RC
and (v)SAA (χ2 analysis, p=0.8). In this study paired samples (PB and
BM) of 25 cases showed a high correlation between the skewing results
in both compartments (Pearson correlation, rr 0.98). Conclusions. In this
study TCR Vβ repertoire analysis did not discriminate between MDS-
RC and (v)SAA. Prospective studies will be necessary to investigate
whether there is a role for this molecular tool in pediatric MDS-RC for
the identification of a subset of patients that is associated with autoimmunity
and therfore could be treated with IST up-front, and whether
it can be used for molecular response monitoring.
0226
INVOLVEMENT OF A T-CELL RECEPTOR REPERTOIRE IN THE PATHOGENESIS OF
MYELODYSPLASTIC SYNDROMES
T. Momot, J. Koenig, A. Ganser, E.-M. Mischak-Weissinger
Medical School Hannover, HANNOVER, Germany
Background and aims. The involvement of a T cell-mediated autoimmune
process in the pathogenesis of the cytopenia in myelodysplastic
syndromes is still under evaluation. To further investigate a T-cell
involvement in the pathogenesis of MDS we have studied the complementarity-determining
region 3 (CDR3) size distribution of the CD3,
CD4 and CD8 T-cell receptor (TCR) V-β-chain subfamilies in the bone
marrow and peripheral blood samples of MDS patients (n=63). Methods.
We used the multiplex PCR based technique TCR spectratyping based
on the size heterogeneity of the CDR3 region and compared the results
with age-matched controls (n=16). Results. TCR V-β skewing of T-cell
repertoire is more frequent in the bone marrow samples of MDS patients
than in the whole blood samples. The most frequently skewing of TCR
V-β fragments occurs in V-β short 1 (28%), V-β short 3 (20%) and V-β
short 5.3 (25%). CD8 T-cells harbour the most pronounced deviations
from a Gaussian distribution of TCR fragment length compared to CD4
T-cells. MDS subtype RA shows a different spectratyping pattern compared
with MDS subtype RAEB. Five of the patients are now far enough
after different types of therapy to evaluate the changes of the spectratyping
pattern. Summary. We conclude that TCR V-β skewing is frequent in
82 | haematologica/the hematology journal | 2007; 92(s1)
MDS especially an CD8 T-cells. Normalization of at least 1 initially
skewed V-β profile after therapy occurred in 5 MDS patients. The analysis
of a potential correlation between response to therapy and normalization
of the TCR repertoire still requires a larger population.
0227
PRACTICAL RECOMMENDATIONS ON THE MANAGEMENT OF HAEMATOLOGICAL
ADVERSE EVENTS IN MDS PATIENTS TREATED WITH LENALIDOMIDE
A. Giagounidis, 1 M. Cazzola, 2 P. Fenaux, 3 G. Mufti, 4 P. Muus, 5
U. Platzbecker, 6 G. Sanz, 7 L. Cripe, 8 M. Von Lilienfeld-Toal, 9 R. Wells10 1 St. Johannes Hospital, DUISBURG, Germany; 2 University of Pavia & IRCCS
Policlinico, PAVIA, Italy; 3 Hopital Avicenne, PARIS, France
4 GKT School of Medicine, LONDON, United Kingdom; 5 University Medical
Center Nijmegen, NIJMEGEN, Netherlands; 6 University Hospital Dresden,
DRESDEN, Germany; 7 Hospital Universitario La Fe, VALENCIA, Spain;
8 Indiana University School of Medicine, INDIANAPOLIS, USA; 9 St. Jamess
University Hospital, LEEDS, United Kingdom; 10 University of Toronto,
TORONTO, Canada
Background. In January 2007, an international group of myelodysplastic
syndromes (MDS) specialists reached a consensus on practical recommendations
regarding the management of Lenalidomide (Len) treatment
in transfusion-dependent intermediate-1/low-risk (IPSS) MDS patients
with del5q. Aims. The presentation of practical recommendations on
the management of haematological adverse events (AE) in MDS patients
treated with Len. Methods. A moderated round table discussion. Results.
In published studies, haematological AE have been the most common
AE and the most frequent reason for dose adjustment. Transient neutropenia
of CTC grade 3 or more occurred in 55%, mostly early in the
treatment phase. Weekly monitoring of full blood count (FBC) is mandatory
for the first 2 months of treatment, and may be continued biweekly
up to 5 months. Biweekly monitoring may be considered thereafter,
depending on haematological status. To prevent severe neutropenia, coadministration
of G-CSF is recommended if the absolute neutrophil
count (ANC) reaches