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

12 th Congress of the European Hematology Association
0510
EFFECTS OF RITUXIMAB ON PERIPHERAL BLOOD STEM CELL MOBILIZATION AND
ENGRAFTMENT IN B CELL NON HODGKINS LYMPHOMA
F. Gaudio, A. Guarini, V. Pavone, T. Perrone, D. Pastore, P. Curci,
A. Giordano, M. Leo, A. Mestice, G. Specchia, V. Liso
Hematology, BARI, Italy
Treatment with rituximab is widely used for B cell non Hodgkin’s
lymphomas (B-NHL). However, its effects on peripheral blood stem cell
mobilization are not completely known. We retrospectively evaluated
52 consecutive B-NHL (30 follicular and 22 diffuse large cells) patients
responding to first-line chemotherapy (CHOP or R-CHOP), but failing
to achieve complete remission (CR). In this group we compared the
mobilization characteristics and engraftment kinetics of 24 patients
receiving and 28 not receiving rituximab six months before PBSC mobilization.
Patients mean age was 37 years (range 17-60). 44 patients
(84.6%) had stage III-IV disease. 34 patients (65.4%) had bone marrow
involvement; systemic B symptoms were present in 30 patients (57.7%).
At the time of PBSC mobilization 32 patients (61.5%) were considered
to be responsive (complete remission, partial remission or sensitive
relapse) and 20 (38.5%) not responsive (refractory relapse or refractory
to therapy). Mobilization chemotherapy consisted of a high dose cytarabine
containing regimen (DHAP) in all patients. The median CD34 + cells
collected was 5.8×106 /kg in patients receiving rituximab vs 7.2×106 /kg
CD34 + cells (p=n.s.) in the non rituximab treated group. Failure to mobilize,
defined as failure to reach a circulating CD34 + cell count of 10/mcl,
occurred in 2 patients (8.3%) in the rituximab group and 3 (10.7%) in
the non rituximab group. All patients were transplanted using myeloablative
chemotherapy conditioning regimen (BEAM); G-CSF was administered
subcutaneously from day +3 at a dose of 5 microg/kg body
weight/day. Comparison of the two groups showed no statistical significant
difference between median days to absolute neutrophil >0.5×109 /L
and platelet >20×109 /L counts after autologous stem cell transplantation,
and no differences in incidence and severity of infections, days of
fever or duration of antibiotic treatment between groups. In conclusion,
the use of rituximab six months before PBSC does not affect the ability
to collect an adequate number of PBSC for autologous stem cell transplantation
in B-NHL. Further studies are warranted in larger populations
to determine the impact of rituximab on collection, engraftment and
survival.
190 | haematologica/the hematology journal | 2007; 92(s1)
Chronic lymphocytic leukemia and related
disorders - Biology II
0511
THE HIGH FREQUENCY OF T REGULATORY CELLS IN PATIENTS WITH B-CELL CHRONIC
LYMPHOCYTIC LEUKEMIA (B-CLL) IS DECREASED BY THALIDOMIDE AND FLUDARABINE
TREATMENT
K. Giannopoulos, 1 M. Schmitt, 2 P. Wlasiuk, 1 J. Chen, 2
A. Bojarska-Junak, 1 M. Kowal, 1 J. Rolinski, 1 A. Dmoszynska1 1 2 Medical University of Lublin, LUBLIN, Poland; University of Ulm, ULM,
Germany
Background. The control of a rather slowly progressing B-cell chronic
lymphocytic leukemia (B-CLL) by the immune system is not yet fully
understood. Several mechanisms underlay the immunosuppressive status
of CLL patients including the excess of T regulatory lymphocytes
(Tregs). The forkhead family transcription factor FOXP-3 is critically
important for the development and function of Tregs. Aims. In current
study we wanted to define the expression of FOXP-3 on CD4 + CD25 high
T lymphocytes in the peripheral blood mononuclear cells (PBMC). Additionally,
we wanted to characterize the influence of Tregs on immune
responses against tumor and viral antigens in the complex system of
PBMC. We also tried to define the influence of thalidomide (THAL)
alone as well as combined with fludarabine (FLU) on Tregs subpopulation
of CLL patients. Methods. In 60 previously untreated patients with
B-CLL the subpopulation of CD4 + CD25 high FOXP3 + T cells that phenotypically
correspond to Tregs was identified. Immunosuppressive function
of Tregs was evaluated in an enzyme-linked immunosorbent spot
(ELISpot) assay to estimate T-cell immune responses against HLA-A2
restricted epitopes derived from tumor associated antigens (TAAs) of
survivin, fibromodulin and RHAMM as well as viral peptide derived
form infuenza matrix protein. Results. The frequency of Tregs was significantly
higher in B-CLL patients compared to healthy volunteers
(HVs) (12.1% vs. 1.9%, p=0.0001). The progressive increase of Tregs
percentages were noted in advanced stages of disease, mean: 9.5% in
stage A, 13.4% in stage B and 15.4% in stage C according to the Binet
classification. Higher frequencies of Tregs correlated with decreased T
cell responsiveness against viral and tumor antigens. Significantly lower
secretion of IFN-γ was observed in patients with higher percentages
of Tregs (more than 11% of the CD4 cells). In 80% CLL patients treated
with THAL + FLU regimen significant reduction of circulating Tregs
after THAL was observed. The combination with FLU resulted in further
decrease of Tregs in 12 of 15 patients. After THAL therapy the
mean reduction was higher in the population of Tregs compared to
whole lymphocyte population (41.2% vs. 19.9%, p=0.046). Higher frequencies
of Tregs were observed in CLL patients with higher levels of
TNF-α serum levels (r2=0.45, p=0.001, n=20). Conclusions. Tregs presented
in high frequencies in B-CLL constitute the crucial immunosuppressive
mechanism among the mononuclear cells of the peripheral blood.
The strategies combining THAL are very promising, since THAL might
target not only the CLL cell population but also Tregs and therefore
restore the CD8 + T cell function. Increased TNF level might promote
Tregs proliferation. Nontheless, the results of our study suggest that
TNF is unable to block suppressive activity of Tregs in B-CLL
0512
B CHRONIC LYMPHOCYTIC LEUKEMIA CELLS EXPRESS THE ORPHAN RECEPTOR
TYROSINE KINASE ROR-1
A.H. Danesh Manesh, 1 E. Mikaelsson, 1 M. Jeddi- Tehrani, 2 A.A. Bayat, 2
R. Ghods, 2 M. Ostadkarampour, 2 M. Akhondi, 2 S. Lagercrantz, 3
C. Larsson, 3 A. Österborg, 3 F. Shokri, 4 H. Mellstedt, 3 H. Rabbani3 1 Karolinska Institute, STOCKHOLM, Sweden; 2 Avesina Research Institute,
TEHRAN, Iran; 3 Karolinska University Hospital Solna, STOCKHOLM, Sweden;
4 Tehran University of Medical Sciences, TEHRAN, Iran
Background. Ror receptors are cell-surface receptors participating in
signal transduction, cell-cell interaction, regulation of cell proliferation,
differentiation, cell metabolism and survival. Ror-1 is a member of the
RTKs family of orphan receptors related to muscle specific kinase
(MUSK) and Trk neutrophin receptors. The human Ror1 is highly
expressed in heart, lung, and kidney but to a lesser extent in placenta,
pancreas and skeletal muscles. In B-CLL a 43.8 fold increase of the
orphan receptor tyrosine kinase (RTK) gene (Ror-1) expression has been
observed previously. Aims. To study the expression of Ror-1 in B-CLL.