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

12 th Congress of the European Hematology Association
0966
EXPRESSION OF CYTOKINE RECEPTORS ON CD34+ BONE MARROW CELLS 100 DAYS
AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION
B. Marianska, J. Kopec-Szlezak, A. Gajewska, J. Wozniak,
I. Szczepanska, K. Halaburda
Institute of Haematology, WARSAW, Poland
After reinfusion, autologous stem cells repopulate bone marrow
promptly. However recovery of their proper function is still poorly
studied. The aim of our investigation was evaluation of expression of
cytokine receptors that are important for haematopoietic progenitors’
engraftment. We compared expression of those receptors in patients’
and normal bone marrow samples. Materials and methods. The study
group consisted of 14 patients 100 days after autologous transplantation.
Normal bone marrow control samples were obtained from
healthy bone marrow donors. CD34 + cells were evaluated according
to standard ISHAGE protocols. Expression of CD184 (CXCR-4 receptor
for SDF-1 chemokine), CD117 (c-Kit, receptor for c-Kit ligand) and
CD114 (G-CSF receptor) on CD34 + cells was studied with CANTO BD
flow cytometer. Commercial monoclonal antibodies stained with fluorochromes
were used. Results. 1/ Higher percentage of CD34 + CD117- cells was found in patients’ samples in comparison to normal bone
marrow (p=0.003), which indicates more progenitors with lymphoidline
commitment. 2/ Higher expression intensity of CXCR-4 receptor
on myeloid progenitors was detected in patients’ samples than in normal
bone marrow (p=0.04) 3/ Stem cell recipients showed lower CD4 +
lymphocyte counts in the blood 100 days after transplantation in comparison
to normal blood samples and as a result lower CD4 + /CD8 +
ratio (0.1-1.4 vs. 1.1-2.8) Conclusion. Our results of cytokine expression
analysis indicate that 100 days after autologous transplantation
regulation of hematopoiesis, and in particular lymphopoiesis, is not
completely stabilized. That may influence abnormal proportion of T
cell subsets in peripheral blood.
0967
CHANGING FROM A FIRST TO SECOND GENERATION IFOSFAMIDE-BASED
CHEMOTHERAPY REGIMEN (FROM IMVP TO ICE) DOES NOT IMPROVE OUTCOME
OF PATIENTS WITH RELAPSED OR REFRACTORY AGGRESSIVE NHL
I. Aurer, 1 Z. Mitrovic, 2 D. Nemet, 1 I. Radman, 1 D. Sertic, 1
R. Serventi-Seiwerth, 1 R. Stern-Padovan, 1 F. Santek, 1 M. Nola, 1
M. Mrsic, 1B. Labar1 1 2 University Hospital Center Rebro, ZAGREB; Medical School, ZAGREB, Croatia
Background. There are no randomized trials comparing different
chemotherapy regimens used for treatment of relapsed or refractory
aggressive NHL. Some years ago very good results have been reported
with a combination of ifosfamide, carboplatinum and etoposide
(ICE). Consequently, a lot of centers started using this regimen. Five
years ago we changed from our previous regimen, consisting of ifosfamide,
methotrexate and etoposide (IMVP), to ICE. Aims. Here we
report our results with ICE and compare them to the results obtained
during the previous five-year period with IMVP. Methods. Patients
with relapsing or refractory aggressive NHL received two cycles of
ICE or IMVP. Responders continued with stem-cell mobilization,
high-dose chemotherapy and autografting. Areas that were not in
complete remission pretransplant were irradiated after hematopoietic
recovery. Results. Forty-five patients were treated with ICE and 28
with IMVP. The percentage of patients with refractory disease was
similar in both groups (22/45 vs. 12/28), while more patients treated
with IMVP had unfavorable IPI scores (16/45 vs. 17/28, p=0,033, ttest).
The response rate (RR) to ICE was 47% (6 patients achieved CR
and 15 PR), 2-year overall survival (OS) 30% and 2-year event-free survival
(EFS) 21%. These results were similar to those obtained with
IMVP (RR 39%, 2-year OS 23%, 2-year EFS 13%, all differences nonsignificant
using t-test and log-rank test) (Figure 1). Toxicity of both
regimens was similar. Sixteen of 45 patients treated with ICE had significant
hematologic toxicity, 12 febrile neutropenia or serious infections
and 3 other serious toxicity (2 neurologic disturbances and one
case of supraventricular tachycardia). Serious hematologic toxicity
occurred in 9 out of 28 patients treated with IMVP, febrile neutropenia
and serious infections in 9 and 1 patient had a tumor-lysis syndrome.
One patient in each group died of treatment-related toxicity.
Conclusions. Changing from a first generation ifosfamide-based regimen,
such as IMVP, to a second generation regimen, such as ICE, does
360 | haematologica/the hematology journal | 2007; 92(s1)
not substantially improve outcomes of patients with relapsed or
refractory aggressive NHL.
Figure 1.
0968
COMPLEX CHROMOSOMAL REARRANGEMENTS IN ADULT PATIENTS WITH AML ARE
INDEPENDENT PROGNOSTIC FACTOR
L. Babicka, 1 Z. Zemanova, 1 J. Brezinova, 2 S. Ransdorfova, 2
L. Pavlistova, 1 M. Siskova, 1 J. Maaloufova, 2 J. Cermak, 2 K. Michalova1 1 General Faculty Hospital and 1st Med Fac, PRAGUE, Czech Republic; 2 Institute
of Hematology and Blood Transf, PRAGUE, Czech Republic
Background and aims. Acquired cytogenetic aberrations are detected in
55-70% of newly diagnosed patients with AML. Most of karyotypic
abnormalities are associated with specific disease subtypes, characteristic
morphologic and immunologic profiles and distinct therapeutic
and/or prognostic implications. However, approximately 10-15% of
AML with abnormal karyotype have no specific aberrations, but do
have complex chromosomal rearrangements (CCR). The aim of the
study was a comprehensive analysis of CCR found in bone marrow
cells of patients with AML or MDS RAEBt at diagnosis by molecular
cytogenetic methods and to evaluate the significance of complex aberrations
for prognosis of these patients. Methods. Karyotypes of all
patients were analysed by conventional cytogenetic method. FISH
analyses were performed according to the result of G-banding using
locus-specific and/or centromeric commercially available probes
(Abbott-VysisTM). Structural and/or complex chromosomal aberrations
were proved by multicolor FISH (mFISH) with the 24XCyte probe kit
with combinatorially labeled painting probes specific for all autosomes
and sex chromosomes (MetaSystemsä). In some cases multicolor banding
(mBAND) was carried out using XCyte-color kits (MetaSystemTM)
for chromosomes 3, 5, 7 and 11. Results. During the years 1998-2006 we
examined 392 patients with AML or MDS RAEBt. We found complex
chromosomal rearrangements at the time of diagnosis in 58 of them
(14,7%). This group included 32 females and 26 males with an average
age 61,2 years, median of overall survival was just 3 months. Only three
patients are living, one after bone marrow transplantation, one in partial
and one in complete remission. The majority of structural abnormalities
were unbalanced. In 50 patients (86%) loss or rearrangements of
chromosome 5, 7 and/or 11 was proved. Deletion of critical regions
5q31 was determined in 35 (60,3%) and deletion 7q31 in 16 (27,5%)
patients. Aberration of MLL gene was found in 11 cases (19%). Trisomy
of chromosome 8 was the most frequent numerical change (11 patients).
Conclusions. Our study demonstrates the clinical importance of cytogenetics
in adult patients with AML. We proved that complex chromosomal
rearrangements are one of the most important prognostic factors,
are associated with very poor prognosis and poor response to
antileukemic treatment. Precise identifications of these aberrations and
delineation of breakpoints in bone marrow cells of patients with AML
at the time of diagnosis could lead to a better understanding of genetic
events during leukemogenesis as well as quiding further molecular studies
of genes involved in evolution of leukemia. We believe that these
findings could provide clinically relevant information that can assist in
the development of risk-adapted therapeutic strategies.
This work was supported by grants MSM LC535, MSM 0021620808,
IGA NR/9227-3