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

unmutated VH genes, and high and low expression of CD38 and ZAP-
70 showed KE. Unmutated VH genes and increased expression of CD38
correlated with KE (p=0.0162 and 0.0299 respectively). Conclusions. Our
data suggest that the effect of KE on prognosis may be a consequence
of genomic instability rather than the acquisition of specific genomic
abnormalities, but this requires confirmation in a large study.
1122
SURVIVAL OF THE LEUKEMIA PATIENTS AMONG CHERNOBYL CLEAN-UP WORKERS
IN UKRAINE
I.S. Dyagil, D.A. Bazyka, V.G. Bebeshko, N.A. Gudzenko,
A.E. Romanenko, N.K. Trotsuk
RCRM, KIEV, Ukraine
Background. Great medical and public concern in Ukraine after Chernobyl
catastrophe was about leukemia as the earliest and the most sensitive
effect of irradiation. The largest epidemiological study on leukemia
risk was initiated in Ukraine by the Research Center for Radiation Medicine
(Ukraine) and National Cancer Institute (USA) to study the
leukemia risks in clean-up workers in Ukraine. One of the important
characteristics of the cases, identified in the framework of the study, is
presented further. Study goal. To study the peculiarities of the leukemia
patients survival among Chernobyl clean-up workers, including life
expectancy, 1-year mortality and 5-year survival rates. Study population.
110 645 male clean-up workers after Chernobyl catastrophe residing in
6 administrative regions of the Ukraine. Period of observation. 1987-2000
Diseases under study. All types of acute and chronic leukemia. Results. The
survival of the 84 of 86 leukemia cases, identified in the study cohort and
confirmed by the International Diagnostic Review Panel in the framework
of the Ukrainian-American retrospective case-control study was
analyzed. Median of the Chronic Lymphocyte Leukemia (CLL) cases
survival was 5 years, of the CML Chronic Myeloid Leukemia (CML)
cases-4 years and Acute Leukemia (AL) cases-3 months. 1-year mortality
rate may be considered as an indicator of the aggressive character of
the disease course. It composed 24% in total and varied from 78% for
AL to 6% for CLL. The proportion has more positive value in compare
with the analogues one for the total Ukrainian population (44% in total).
5-year survival rate composed in total 43% with highest value (53%) for
CLL and lowest (1 of 18) for AL. The same value was identified for the
total Ukrainian population (41,7-45,9% in total). Conclusions. Relatively
lower 1-year mortality rate in leukemia cases among clean up workers
in compare to Ukrainian population does not prove the less aggressive
disease course. It may demonstrate more high level of the diagnostic
and treatment of sufferers following Chernobyl catastrophe. Similar 5year
survival rate in clean-up workers and general population may serve
as proof of this.
1123
IDENTIFICATION OF A NOVEL, TRANSACTIVATION-DEFECTIVE SPLICING VARIANT OF P53
GENE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
S.P. Pekova, 1 R. Cmejla, 2 L. Smolej, 3 T. Kozak, 4 M. Spacek, 4 M. Prucha1 1 Na Homolce Hospital, PRAGUE; 2 Inst. of Hematol and Blood Transfusion,
PRAGUE; 3 Department of Clinical Hematology, HRADEC KRALOVE; 4 Dept.
of Clin Hematol , Faculty Hospital, PRAGUE, Czech Republic
Background. p53 is an important protein implemented in many cellular
processes controlling the cell fate. It has been reported that besides
the well-studied regulation of p53 at the levels of protein-protein interactions
and posttranslational modifications, the activity of p53 is substantially
controlled at transcriptional level, too. Aims and methods: In our
group of 397 patients with chronic lymphocytic leukemia (CLL), we
have investigated mutational status of p53 gene using direct sequencing.
All identified mutations were tested by a functional assay FASAY (Functional
Analysis of Separated Alleles in Yeast). Results. In 25 out of 397 cases
(6.3%), point mutations or short deletions were found. Using cDNA
sequencing, a novel p53 splicing variant, lacking the whole coding
sequence of exon 6 was identified. This splicing p53 isoform (delta ex6)
lacks the original 113 nucleotides of exon 6, thus leading to a frame shift
mutation and premature STOP codon after 189th amino acid. The delta
ex6 p53 variant is devoid of transactivational activity and is differentially
expressed in CLL patients as compared to healthy controls. Summary
and conclusions. Herein, we present evidence of a novel delta ex6 p53 splicing
variant that is differentially expressed in patients with CLL. This
finding supports the recent data on dysregulation of p53 splicing pattern
in malignancies.
12 th Congress of the European Hematology Association
1124
ASSOCIATION BETWEEN PREVALENCE OF FRACTURES AND BONE MINERAL DENSITY
IN SURVIVORS OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA
M. Krawczuk-Rybak, K. Muszynska-Roslan, J. Krawczuk-Rybak,
J. Konstantynowicz
Medical University, BIALYSTOK, Poland
Since children and adolescents are at the most rapidly developing
stages of their lives when childhood cancer is diagnosed, the disease and
its therapy can severely disturb the normal growth, bone mineral acquisition
and skeletal development. In adults a deficit of 1 SD in bone mass
is associated with a 1,5-3-fold increased incidence of fracture. So far, no
correlation between BMD and fracture risk in children, especially in cancer
survivors, has been determined. The aim of the study was to determine
the prevalence of fractures and to asess an association between
bone mineral density and fractures in survivors of acute lymphoblastic
leukemia in childhood Material and methods. One hundred and seven (70
males) survivors of acute lymphoblastic leukemia (median age at diagnosis
7.3 years) were assessed in this study, they recevied: chemotherapy
with methotrexate and antymetabolities, glucocorticoids and in parts
(n=62) cranial irradiation (12 Gy). We acknowledged only the treatment
elements of a previously evidenced negative influence of bones. All fractures
events were documented by x-ray. Information on age at the time
of fractures, trauma severity and anatomical location was obtained from
a detailed questionnaire. Using dual-energy x-ray absorptiometry bone
mineral density (BMD) of spine and total body were performed twice :
after a completed treatment (median age 10.3 years) and after a 1,5 year
follow-up period (median age 11.8 years). The references values were
obtained from the 473 age- and gender-matched healthy children from
the north-east region of Poland. The results were expressed as Z-score.
Results. Forty one subjects (38.1% of the studied population) had a history
of fractures. Six of them were patients presenting with vertebral
compression fractures at the time they were diagnosed of ALL. Twenty
eight subjects reported their fractures had occurred after treatment. All
fractures (except for those of vertebral bodies) were localized in the
extremities (65.6% in upper: wrist, radius, ulna or ankle and 34.3% in
lower extremities: tibia, humerus); all of them were results of injuries,
including low-energy trauma. BMD Z-score for total body (mean -0.11
and '0.012) and BMD Z-score for lumbar spine (mean 0.03 and '0.10)
were not significantly different from reference values in both examinations.
No significant difference in BMD Z-score between patients reporting
fractures compared to the non-fractured subjects was found. No associations
were found between BMD and cranial irradiation, cumulative
dose of steroids, high dose of metothrexate or fracture prevalence.
Changes in BMD accrual did not correlate with any parameters of treatment.
Conclusions. 1. In survivors of childhood ALL prevalence of fractures
was not associated with lower BMD. 2. Pattern of fractures was similar
to the published data in healthy population. 3. Further studies in this
area are needed to determine a long-term effect of cancer therapy on
bone mass and bone fragility.
1125
LENALIDOMIDE TREATMENT AND THE EFFECTS ON T-CELL RECEPTOR REPERTOIRE
IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES (MDS)
T. Momot, J. Koenig, A. Ganser, E.-M. Mischak-Weissinger
Medical School Hannover, HANNOVER, Germany
Background and aims. The myelodysplastic syndrome (MDS) is a multifactorial
pathogenetic disease and therefore therapeutic decisions in
patients with MDS are very complex. A novel immunomodulatory drug
for the management of 5q-subtype of MDS is lenalidomide. This agent
shows encouraging results in MDS treatment. 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 5q-subtype of MDS
patients before and after therapy with lenalidomide (n=10). 6/7 MDS
patients treated with lenalidomide and evaluable to date achieved a CR
(complete remission), one a PR (partially remission). Methods. We used
the multiplex PCR based technique TCR spectratyping based on the size
heterogeneity of the CDR3 region and compared the results with agematched
controls (n=10). At the same time we collected urine samples
of these patients for proteome analysis. Summary. We confirmed that
TCR V-β skewing of T-cell repertoire is more frequent in the bone mar-
haematologica/the hematology journal | 2007; 92(s1) | 413