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

1105
CYTOGENETIC ABNORMALITIES IN 350 PATIENTS DIAGNOSED WITH B-CELL CHRONIC
LYMPHOCYTIC LEUKEMIA AND RELATIONSHIP WITH IGVH MUTATIONAL STATUS
J.A. Hernández, 1 P. Martín-Jiménez, 2 M. Sierra, 2 V. Sandoval, 3 R. Fisac, 3
A. García de Coca, 3 M. Romero, 3 I. Recio, 3 J. Galende, 3 A. González-
Serna, 3 G. López-Núñez, 3 R.M. López, 3 F. Ortuño, 3 L. García-Frade, 3
M. González, 2 J.M. Hernández 2
1 Hospital de Fuenlabrada, FUENLABRADA; 2 Hematology, CIC, SALAMAN-
CA; 3 Hematology, LEÓN, Spain
Background. In the last years, a better characterization of the biology
of CLL based on molecular studies has been ascertained. Thus, the presence
of some chromosomal abnormalities and IgVH mutational status
identify patients with different clinical and prognostic course. Aims. To
determine by FISH the most prevalent cytogenetic aberrations of CLL-
B. To correlate the results with the mutational status of the immunoglobulin
VH genes. To analyze survival and time to the first therapy. Methods.
A total of 350 patients diagnosed with CLL-B (233 male; ratio: 2,0)
were included. Median age was 65 years (range: 29-90). Median WBC:
20×10 9 /L (range: 5.3-370). LDH > 1n = 13.4%. β2microglobulin > 1n =
33.7%. Diffuse bone marrow pattern: 28.3%. Binet A stage: 79% of
patients. In FISH study, specific probes of 13q14, +12, 11q21, 14q32 and
17p13 were used. Mutational status was performed in 155 cases. Unmutated
cases were considered when a VH homology ≥ 98% was present.
Results. A total of 235 patients (66.2%) presented with, at least, a cytogenetic
abnormality: del (13q): 156 pts (45.6%), +12: 39 pts (11.3%), del
(11q): 28 pts (8.3%), del (17p): 15 pts (4.4%), IgH rearrangements: 18 pts
(6.2%) (with BCL1/IGH fusion negative in all cases), others: 3 pts (<
1%). In 48 cases (13.7%), ≥2 cytogenetic aberrations were observed.
Eighty-two patients showed a mutated pattern (52.5%). Median followup
was 38 months. The variables related to shorter survival in the univariate
analysis were: del(11q), del(13q), del(17p), unmutated status, sex
(male), Coombs test + , high LDH, high β2microglobulin, splenomegaly,
advanced Binet stage, diffuse pattern and CD38 + . By contrast, in the
multivariate analysis only a high β2microglobulin level and del(17p)
were associated with a poor survival. Del(11q) or del(17p) were associated
with an unmutated status or CD38 + , while cases with del(13q) had
a mutated IGH or CD38-. Median survival times (in months) of the different
cytogenetic categories were: del(17p): 50 m, del(11q): 74 m, +12:
99 m, del(13q): 154 m, and normal karyotype: not reached. Survival of
mutated patients was better (p=0.018) (median survival time nor reached
in both groups). The multivariate analysis showed the following factors
as negatively related to the survival (Odds Ratio): del(17p) (6.83), del(11q)
(2.69), del(13q) (0.26), IGH mutation (0.24), while the parameters influencing
the time (in months) to first therapy were: del(17p): 3 m, del(11q):
10 m, +12: 26 m, normal karyotype: 65 m, del(13q): 87 m; unmutated
cases: 22 m, mutated cases: 107 m. Mutation status, Binet stage, diffuse
pattern and p53 status were selected in multivariate analysis. Summary.
The associations between del(13q)/mutated status and del(11q) or
del(17p)/unmutated cases were confirmed. The presence of IGH abnormalities
(6.2%) supports the inclusion of this parameter at the diagnosis
of CLL patients. Overall survival and therapy free interval were significative
related with the genetic abnormalitites of CLL.
Partially financed by a grant of Consejería de Sanidad de Castilla y León
(106/A/06)
1106
AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION AS AN UP-FRONT
THERAPY IN MULTIPLE MYELOMA: THE LEBANESE EXPERIENCE
A. Bazarbachi, 1 Z. Otrock, 1 A. Mugharbel, 2 R. Mahfouz, 1 Z. Salem, 1
W. Shebbo, 2 H. Hatoum, 1 G. Nsouli, 2 A. Shamseddine, 1 R. Jalloul, 2
A. Taher, 1 N. El-Saghir, 1 E. Baz, 1 J. Makarem, 1 A. El-Kinge, 1 S. Okaily, 1
N. Droubi, 1 N. Kreidieh, 1 N. Yassine, 2 T. Jisr, 2 A. Ibrahim2 1 2 American University of Beirut, BEIRUT; Makassed Hospital, Beirut, BEIRUT,
Lebanon
Background. Autologous stem cell transplantation (ASCT) has become
the gold standard therapy for young patients with multiple myeloma.
Aims and Methods. We report the results of ASCT used as up-front therapy
in 71 patients with stage III (Durie-Salmon) multiple myeloma autotransplanted
between March 1997 and October 2006 in the two major
bone marrow transplantation units in Lebanon. Results. Median age of
the patients was 49 years (29-70). There were 49 males and 22 females.
Twelve patients (17%) were in stage IIIB. IgG, IgA and light chain were
the most frequent types (58%, 21% and 17% respectively). Sixty-six
patients (93%) received VAD protocol (3-6 cycles) and 4 patients (6%)
received thalidomide + dexamethasone. Seventy patients received autologous
peripheral stem cell transplantation (APSCT). Cyclophosphamide
(4-5 g/m 2 ) followed by G-CSF (10µg/kg/day) were given for peripheral
stem cell mobilization. The median number of CD34 + cells collected
was 10.24×10 6 /kg (1.36-60). High dose chemotherapy consisted of Melphalan
which was given at a dose of 200 mg/m 2 in 60 patients (85%);
the others received Melphalan at a dose of 140 mg/m 2 . Fifty-nine patients
(83%) underwent one ASCT and 12 patients (17%) underwent tandem
ASCT. The median number of CD34 + cells transplanted was 5.79× 10 6 /kg
(1.36-20) per transplant for the patients who underwent APSCT. Bisphosphonates
were given IV to all patients for about 2 years after ASCT.
Response was assessed according to the EBMT criteria (Blade J. et al., Br
J Haematol, 1998. 102: 1115-1123). Disease status before ASCT was as
follows: 8 patients (11%) were refractory, 4 patients (6%) had minimal
response, 54 patients (76%) had partial response and 5 patients (7%)
were in complete remission (CR). Transplantation-related mortality rate
was 1.4%. Twenty-one patients (30%) were in CR after ASCT. Thirtysix
patients (51%) who relapsed or progressed after ASCT received
thalidomide±dexamethasone (30 patients), a second ASCT (4 patients)
and Velcade (2 patients). The median overall survival (OS) and the median
progression-free survival (PFS) were 60 and 32 months respectively
(Figure 1). Conclusion. The feasibility of APSCT for multiple myeloma in
Lebanon was acceptable with an OS and PFS rates comparable to the
EBMT registry.
Figure 1. Overall survival curve.
12 th Congress of the European Hematology Association
1107
THE EXPRESSION OF MDR1 PROTEIN IN DE NOVO ACUTE MYELOID LEUKEMIA WITH
NORMAL KARYOTYPE
M. Cioch, J. Kocki, M. Jarosz, A. Dmoszynska
Medical University of Lublin, LUBLIN, Poland
Introduction. The normal karyotype is detected in 40-45% of adults
with acute myeloid leukemia (AML). These patients belong to an intermediate
cytogenetic group. The additional factors are needed to predict
the therapeutic outcome. The well established risk factor for treatment
failure in patients with AML is expression of MDR1 (Multidrug Resistance
1) gene in leucemic blasts, that encodes a 170-kd transmembrane
glycoprotein, known as P-glycoprotein (P-gp). The aim of this study was
evaluation of MDR1 expression significance as a factor discriminating
prognostic subgroups in AML with normal karyotype. Material and methods:
One hundred and twenty one patients (pts: 60 males and 61 females;
ranged from 18 to 82 years-mean 51.2) were included in the study. They
were treated with induction therapy acc. Polish Adult Leukemia Group
(PALG) programme. Cytogenetic analysis was performed on bone marrow
aspirates by tripsin-Giemsa banding technique and the ambiguous
cases were additionally analysed by FISH method with using probes for:
t(15;17), t(8;21), inv(16), t(v, 11q23), aberrations of chromosome 5, 7, 8
and 20. MDR1 (Pgp-170) expression was measured by labelling fresh
viable bone marrow cells with UIC2 PE monoclonal antibody
(Immunotech) and analysis in FACSCalibur flow cytometer. Results.
Among 121 pts, 109 (90.1%) had information from a cytogenetic analy-
haematologica/the hematology journal | 2007; 92(s1) | 407