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

1099
ALTERATIONS IN THE NATURAL KILLER CELL REPERTOIRE IN MYELODYSPLASTIC
SYNDROMES
B. Baumann, M. Jädersten, A.M. Forsblom, M. Jansson, E. Hellström-
Lindberg, H.G. Ljunggren, K.J. Malmberg
Karolinska Institutet, STOCKHOLM, Sweden
Background. Myelodysplastic Syndromes (MDS) constitute a group of
clonal stem cell disorders characterized by ineffective hematopoiesis
and pancytopenia. The only curative treatment for MDS is allogeneic
stem cell transplantation (SCT). Several studies have shown that NK
cells play an important role for the outcome of SCT in patients with
myeloid malignancies. These results suggest that NK cells may constitute
an important therapeutic tool in the treatment of hematological diseases
such as MDS. Aim. The aim of this study was to investigate the NK
cell repertoire in MDS patients with regard to receptor expression, function
and cytogenetic aberrations. Methods. Bone marrow (BM) and
peripheral blood (PB) was collected from 25 patients of different MDS
subgroups and 16 healthy control donors. NK cells were analyzed for
their receptor repertoire using multicolor flow cytometry. Interphase
fluorescence in situ hybridization (FISH) was performed on purified NK
cells from patients with 5q- syndrome to detect deletions in chromosome
5. Results. MDS patients of all subgroups displayed severe alterations in
their NK cell receptor repertoire with decreased expression of several
activating NK cell receptors including DNAM-1, NKp46, and CD16.
These alterations were confined to BM-derived NK cells and did not
affect NK cells in PB. Two patients had abnormally high levels of
CD56bright NK cells displaying a reversed ratio between CD56bright
and CD56dim NK cells with 75% and 50% regulatory CD56bright NK
cells in BM and PB, respectively. Interphase FISH revealed that a subgroup
of NK cells in 5q- syndrome patients displayed the cytogenetic
anomaly existing in myeloid cells. Conclusions. Our results show that
MDS patients display several phenotypic aberrations in their NK cell
repertoire with a predominant loss of activating NK cell receptors. In
patients with 5q- syndrome, the deletion of chromosome 5q was found
in a subgroup of NK cells. Altogether, these results may have implications
for pathogenesis of MDS and response to immunomodulatory
treatments.
1100
LIPOSOMAL DAUNORUBICIN AND POLYETHYLATED GLYCOL
CONJUGATED ASPARAGINASE (PEG-ASPA) IN CHILDREN WITH RELAPSED AND
REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA TREATED ON COMPASSIONATE BASIS
M.S. Sedky, 1 J.P. Vannier, 2 G. Leverger, 3 K. Yakouben, 4 D. Adjaoud, 3
E. Vilmer, 4 A. Baruchel5 1 Hôpital Robert Debré, PARIS; 2 CHU de Rouen, ROUEN; 3 CHU Armand
Trousseau, PARIS; 4 CHU Robert Debre, PARIS; 5 CHU Saint-Louis, PARIS,
France
Background. Daunoxome (DNX) is an encapsulated form of daunorubicin
in liposomal vesicles with suggested better pharmacokinetics, pharmacodynamics
and lesser cardiotoxicity than the free form. Polyethyl
glycol (PEG) asparaginase (PEG-ASPA), a modified form of L-asparaginase,
has a better activity and a lesser immunogenicity than its native
molecule. Aim. To evaluate on a compassionate basis, the combination
of Daunoxome and PEG asparaginase as regard to efficacy and toxicity
as a salvage treatment in refractory/relapsed childhood ALL Methods.
The combination of these 2 drugs has been used in 9 relapsed or refractory
ALL children. One child was refractory after 2 lines of chemotherapy,
7 children and one child were in 2nd and 1st relapse respectively. A
salvage therapy used DNX on the basis of weekly 3 doses Day (D) 1, 8,
15: 100 mg/m 2 /dose. PEG-ASPA single dose 2500 IU/ m 2 /dose, D 15.
Vinca alkaloids and corticosteroids were associated. Results.The median
duration of hospitalization was 4 days (0-55). Complications were mainly
neutropenia grade IV n=4, grade III infection n = 6, grade II cardiac toxicity
n = 1, grade III allergy, grade III hemostasis disorders, thrombosis,
n = 1 respectively. All patients achieved CR except one. Eight out of 9
were subjected to hematopoietic stem cell transplantation (HSCT). In
total, one patient died before transplant from disease progression and out
of the remaining 8 undergoing HSCT. Two patients are alive and well,
4 died from transplant related causes and 2 from disease progression.
*Conclusion.* Salvage treatment of advanced childhood ALL by DNX and
PEG-ASPA with steroids and vinca-alcaloids is feasible as regard to toxicity.
This small patient sample with very advanced disease suggests an
interesting response rate, allowing to proceed to HSCT and possible
cure.
12 th Congress of the European Hematology Association
1101
CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS EXPOSED TO IONIZING RADIATION DUE
TO THE CHERNOBYL NPP ACCIDENT WITH FOCUS ON IMMUNOGLOBULIN HEAVY CHAIN
GENE ANALYSIS
N. Bilous, 1 I. Abramenko, 2 A. Chumak, 2 E. Davydova, 3 Z. Martina, 2
I. Kryachok, 2 D. Bazyka, 2 V. Bebeshko 2
1 Research Center for Radiation Medicine, KIYV, Ukraine; 2 Research Centre for
Radiation Medicine, KIYV, Ukraine; 3 Center of Veterinary Medications,
MOSCOW, Russian Federation
Some epidemiological data suggest about weak relation between
development of chronic lymphocytic leukemia (CLL) and influence of
ionizing radiation (IR). Since restricted number of mechanisms should
realize assumed influence of IR on CLL development we hypothesized
that CLL in IR-exposed patients may be a more homogeneous disease
with regard to its immunoglobulin variable heavy chain (IGHV) gene
usage and somatic hypermutation status. Using sequence analysis of
polymerase chain reaction products, the IGHV gene’s configuration was
analyzed in 44 CLL patients previously exposed to IR due to Chernobyl
NPP accident (32 clean-up workers, 8 inhabitants of radionuclide contaminated
areas and 4 evacuees) in comparison with 119 IR non-exposed
patients of control group. It was found the prevalence of unmutated cases
in both groups (76.2% and 70.6%, respectively). Whereas IR-exposed
patients were unselected and the most of them (82%) observed from the
beginning of disease, control group was presented by more severe inpatients
cases, that was confirmed by such data as shorter period from
diagnosis and beginning of therapy (median 7 months in comparison
with 24 months in IR-exposed patients; p=0.04), higher initial WBC
counts (73.4 and 45.8×10 9 /L ,respectively; p=0.007), tendency for worse
overall survival (medians 96 and 137 months, respectively; p=0.053).
The higher number of unmutated cases was found in clean-up workers
of 1986 year (94.1%), who belong to the most suffered contingents due
to Chernobyl NPP accident. The distribution of IGHV gene family in IRexposed
patients did not differ from others CLL cohorts in USA and
Europe, while in control group increased number of IGHV1 genes usage
was revealed. Cases with homologous sequences were found in 28.5%
of IR-exposed and 29.4% of IR non-exposed patients that related to subsets
#1, 2, 3, 5, 6, 7, 9, 11, 12, 19, 25, 28, 34. Another feature of IRexposed
cases was increased number of the secondary development or
coexistence of solid tumors and CLL (7 cases, 15.9%) in comparison
with the control group (3 cases, 2.5%). Six solid tumors were diagnosed
in clean-up workers of 1986 year. In the whole, 11 IR-exposed patients
had solid tumor or Richter transformation (one patient had basal cell
carcinoma and then Richter transformation was developed) compared to
8 patients in control group (p=0.001). These preliminary data suggest
that CLL in IR-exposed persons, especially in clean-up workers of 1986
year has some distinguish features from CLL in IR non-exposed patients
that it is necessary to confirm in more extensive study.
1102
INFLUENCE OF TREATMENT FOR ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
AND NON- HODGKIN LYMPHOMA (NHL) DURING CHILDHOOD ON TESTICULAR
FUNCTION
M. Krawczuk-Rybak, E. Solarz, A. Gadomski, M. Matysiak,
M. Wojtkowska
Medical University, BIALYSTOK, Poland
Endocrine abnormalities including gonadal dysfunction are common
late effects of anticancer treatment. Chemo- and radiotherapy affect
both components of gonadal function: steroidogenesis and spermatogenesis
resulting in infertility and sexual dysfunction which may compromise
quality of life of the survivors.This problem is well known in
patients treated for Hodgkin lymphoma with the use of the alkyling
agents and radiotherapy for abdomen; less is known about the patients
treated for ALL and NHL. There are also unambiguous opinions on the
problem: if the testicular damage after anticancer treatment is similar in
boys treated in prepubertal and pubertal stage. In this study we evaluated
the gonadal function in young adults after the treatment for hematological
malignancies; especially we analysed the values of inhibin B as
a marker of spermatogenesis. Patients and Methods. Thirty one adolescents
at mean age 17.7±2.2 (Tanner IV and V) treated for ALL (n=19) and
NHL (n=12) 6.0±3.5years before; twenty of them were treated before
puberty (at mean age 7.05±3.33) and eleven-during puberty
(14.93±1.5).Thirteen received radiotherapy for central nervous system
(CNS) -12 or 18Gy. We evaluated serum levels of inhibin B, testosterone,
follicle-stimulating hormone (FSH) and lutenizing hormone (LH) and
haematologica/the hematology journal | 2007; 92(s1) | 405