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

12 th Congress of the European Hematology Association
with busulfan. Complete donor chimerism was achieved at 30 days
after transplantation in 12 patients (10 allo-HSCT, 2 RIC). Mixed donor
chimerism was achieved in the rest patients (7 RIC). Only 3 patients
developed acute GVHD grade > 2. Overall survival evaluated on 100 day
was 95%. Overall survival and disease-free survival with a median follow
up of 19 months rates was 95% and 85% respectively. Conclusions.
Once-daily administration of intravenous busulfan administrated with
cyclophosphamide or fludarabine was effective and had short toxicity.
1280
CD52 ANTIGEN IS EXPRESSED AT DIFFERENT INTENSITIES ON TUMOR CELLS
OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA, SMALL LYMPHOCYTIC
LYMPHOMA, MANTLE CELL LYMPHOMA AND ON CD34+ CELLS
M. Klabusay1 , V. Sukova1 , P. Coupek2 , Y. Brychtova1 , J. Mayer1 1 2 University Hospital Brno, BRNO, Czech Republic; Czech Geology Survey,
BRNO, Czech Republic
Background. Monoclonal antibody anti-CD52 (Campath-1H) is used
for treatment of B- and T-lymphoproliferative diseases. The success of
the treatment is influenced by, among other factors, the target antigen
expression level on tumor cells. Small lymphocytic lymphoma (SLL) and
B-cell chronic lymphocytic leukemia (B-CLL) are often considered as
two clinical manifestations of one type of disease. The presence of CD52
antigen on CD34 + cells is not yet clear and quantitative flow cytometry
could contribute to its clarification. Aims. The goal of the work was to
analyze the expression intensity of the CD52 antigen in patients with
B-CLL, mantle-cell lymphoma (MCL) and SLL and to compare them
with CD52 expression on B-lymphocytes of a healthy population and
CD34 + cells in peripheral blood stem cells (PBSC) grafts. Methods. Recently
diagnosed and previously untreated patients were evaluated. Furthermore,
expression of CD52 antigen on CD34 + cells from graft of PBSC
was analyzed. The CD52 antigen level was measured on tumor cell
populations in patients and on the B-lymphocytes of a control group.
The intensity of expression was expressed in molecules of equivalent
soluble fluorochrome units (MESF) and antibody binding capacity
(ABC). Results. In the group of patients with chronic lymphocytic
leukemia, the CD52 level on B-CLL lymphocytes (245000 MESF; 107000
ABC) was significantly lower than on B-lymphocytes of the control
group (446000 MESF; 194000 ABC; p3000/µL or neutrophil count > 1500/µL, and the evidence
464 | haematologica/the hematology journal | 2007; 92(s1)
of infection induced severe neutropenia. Safety was assessed by clinical
signs and symptoms of adverse events. Results. Severe leukopenia and
or neutropenia could be observed at the first, second, third, fourth, fifth,
and sixth cycles of chemotherapy, and in 44% of cases this adverse
events occurred at the first cycle. The administration of rHu-GCSF was
followed by leukocytosis (median: 18,350/µL; range: 3,100-68,700/µL)
and neutrophilia (median: 14,225/µL, range: 1,600-61,200/µL). Severe
leucopenia or neutropenia mostly occurred for 2 days (39%) with the
duration mean was 2.32±1.30 days. Mostly, rHu-GCSF was administered
for 2 days (26%) and 3 days (28%) to increase leucocyte count
>3000/µL or neutrophil count >1500/µL. Infections (febrile neutropenia,
stomatitis, acute respiratory infection) developed in leucopenia /
neutropenia state before the administration of rH-GCSF were observed
in 39.58% of 54 cycles. However, after the administration of rH-GCSF
no mortality was reported due to those infections . The adverse events
suggested due to rH-GCSF included bone pain (5 patients) and fever (5
patients). Eight patients experienced serious illness. Five patients were
hospitalized due to the thrombocytopenic bleeding and stress ulcer and
3 patients died of the disease progressiveness. However, all those serious
illness were not related to the rHu-GCSF administration. Conclusion.
The administration of the more affordable rHu-GCSF has shortened the
duration of leucopenia / neutropenia as well as has demonstrated the
efficacious and safe treatment of severe chemotherapy induced leucopenia/neutropenia
in Indonesian population.
1282
KARYOTYPIC AND FLUORESCENCE IN SITU HYBRIDIZATION (FISH) ANALYSES OF
CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA AT DIAGNOSIS: THE GREEK PROFILE
V.G. Georgakakos, 1 C. Stavropoulou, 1 A.P. Parcharidou, 2 K. Manola, 1
V. Papadakis, 2 S. Polychronopoulou, 2 E. Patsouris, 3 G. Pantelias, 1
C. Sambani1
1 2 N.C.S.R. Demokritos, ATHENS; Aghia Sofia, Children’s Hospital, ATHENS;
3University of Athens, Medical School, ATHENS, Greece
Background. Acute lymphoblastic leukemia (ALL) represents about
85% of childhood leukemias. The current cure rate is nearly 80%,
reflecting the remarkable progress in identifying and treating resistant
subtypes of the disease. A large number of established structural and
numerical chromosome rearrangements have now been described, for
which the underlying genetic alterations and prognostic significance are
well known. These include the t(12;21) with the TEL/AML1
(ETV6/RUNX1) fusion, hyperdiploidy ≥50, p16 gene (9p21) deletion and
rearrangements of 11q23 involving MLL. Aims. We investigated the
cytogenetic profile of pediatric ALL in Greece. The karyotypic findings
were integrated with the interphase FISH results and further explored
by metaphase FISH. Patients and Methods. Sixty eight Greek pediatric
patients with ALL at diagnosis (64 B-ALL, 4 T-ALL) were included in the
study. The age ranged from 1 to 17 years and the male to female ratio
was 3:2. Bone marrow specimens were initially studied by conventional
cytogenetics and further tested by FISH for the presence of the
TEL/AML1 fusion gene, rearrangements of the MLL gene, p16 (9p21)
gene deletion and hyperdiploidy. The molecular cytogenetic study was
conducted (interphase FISH, iFISH; metaphase FISH, mFISH) using the
commercially available probes LSI TEL/AML1 ES Dual color translocation,
LSI MLL Dual color Break Apart rearrangement, LSI p16 (9p21)/CEP
9 Dual color (Vysis, Downers Grove, IL, USA) and a-satellite probes specific
for the centromere of chromosomes 4, 6, 10, 17, 18, X (Vysis,
Downers Grove, IL, USA) and chromosomes 13, 16 and 21 (Cytocell,
Cambridge UK). Results. Conventional cytogenetic analysis was successful
in 61/68 cases (89.7%) and detected clonal abnormalities in 22/61 cases
(36.1%). FISH revealed that 13/68 (19.1%) patients were positive for
the TEL/AML1 fusion gene. Additional genetic changes were present in
9/13 (69.2%) of the TELAML1 + cases and consisted of deletion of the
unrearranged TEL gene (5/13, 38.5%), an extra der(21)t(12;21) (4/13,
30.8%), an extra AML1 gene (3/13, 23.1%) and heterozygous deletion
of the MLL gene (2/13, 15.4%). More than one additional genetic change
was observed in 2/13 (15.4%) of these cases. Moreover, using the
TEL/AML1 probe we detected one case 1/68 (1.47%) carrying amplification
of the AML1 gene. The p16 gene deletion occurred at an incidence
of 20.7%, while no structural MLL rearrangement was detected in our
sample. The use of centromeric probes revealed clones with hyperdiploidy
in 20/68 patients (29.4%). Overall, combining karyotypic analysis
with FISH, the abnormality detection rate was increased to 70.6%.
Summary/Conclusions. Our cytogenetic study on Greek pediatric ALL suggests
that the incidence for the most common chromosomal abnormalities
are very similar to those reported in the literature. The detection of
secondary genetic changes in TEL/AML1 + cases at diagnosis may imply