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

12 th Congress of the European Hematology Association
0,001). The mean annual number of cases is 180 (104 AML, 75 ALL), and
it varies from 166 to 197 per year. The monthly number of cases is 150,
and it varies from 121 cases in September to 179 cases in May, the difference
is not significant. The number of cases at different ages shows
a great incidence at the ages of 0-5 years (11%), 6-10 years (11,8%) , 11-
15 years (11,4%), and 16-20 years (10,9%). As compared with the incidence
at older ages, the difference is statistically significant. When the
cytological types are considered, we noted that for the ALL, the type L1
was the most frequent, (63,9%), the difference between type 1 and type
2 incidences is statistically significant (p3 for 100 000 habitants). This is probably
because a number of cases of AML in old patients are not diagnosed and
not recorded. In contrast, the incidence of ALL in our series is very close
to that reported in the literature.
1299
JAK2 MUTATIONAL STATUS IN THE DIAGNOSTIC WORK-UP OF PATIENTS
WITH SPLANCHNIC VEIN THROMBOSIS
E. Ammatuna, 1 L. Bellis, 2 T. Ottone, 1 V. Forte, 1 F. Agostini, 1 L. Giannì, 1
S. Lavorgna, 1 S. Faccia, 1 E. Cotroneo, 1 M. Mirabile, 1 A. Riccitelli, 1
M.C. Petti, 3 S. Amadori, 1 L. De Felice, 1 F. Lo-Coco1 1 Policlinico Universitario Tor vergata, ROME; 2 Divisione di Gastroenterologia
Ospedale, MARINO; 3 Ematologia, Istituto Regina Elena, ROMA, Italy
Background. Splanchnic vein thrombosis (SVT) including Budd-Chiari
syndrome (BCS) and extrahepatic portal vein obstruction, is associated
with thrombophilic abnormalities and/or underlying chronich myeloproliferative
disorders (CMPD). Whereas the diagnosis of thrombophilia
is relatively simple, that of CMPD is sometimes difficult due to concomitant
hypersplenism and/or hemodilution, that mask the clinical and
laboratory features of classic CMPD. Using the classical criteria for the
diagnosis of polycythemia vera (PV), essential thrombocythemia (ET),
and idiopathic myelofibrosis (IMF), an overt CMPD can be recognized
in about 30% of patients with SVT, while in 25% of patients no underlying
cause is found and these forms are therefore referred to as idiopathic
SVT. However, based on the results of erythroid and megakaryocytic
colony studies, it has been suggested that latent CMPD can be identified
in about 80% of idiophathic SVT. Recently, a novel point mutation in the
autoinhibitory JH2 domain of the JAK2 gene (V617F) has been found in
about 90%, 75% and 50% of PV, ET and IMF patients, respectively. The
high specificity of such genetic lesion for CMPD can be used for the diagnostic
work-up of occult CMPD in SVT patients.
Table 1.
Aims. The aim of this study was to evaluate the incidence of occult
CMPD in a cohort of 18 patients with idiopathic SVT. Methods. DNA was
extracted from peripheral blood and the JAK2 mutational status was
investigated by allele specific PCR. All patients were negative for throm-
470 | haematologica/the hematology journal | 2007; 92(s1)
bophilia screening including genotyping for prothrombin (G20210A), and
factor V Leiden (G1691A) mutations, anti-phospholipid antibodies,
hyperomocysteinemia, and antigenic assay for protein C and S and ATI-
II. SVT was diagnosed by doppler ultrasonography, CT-scan or venography.
Results. The main clinical data, JAK2 mutational status and results
of endogenous erythroid colony (EEC) study in the analysed series are
shown in the Table 1. All patients had normal blood counts. The JAK2
V617F was detected in 8/18 patients, including 5/8 with BCS and 3/4
with portal vein thrombosis. In JAK2 mutated cases, EEC were positive
in 3/5 patients with BCS and 2/3 patients with portal vein thrombosis.
EEC were negative in all patients wild type for JAK2. Bone marrow histology
was performed in 6 patients, (5 JAK2V617F and 1 JAK2 wild type)
and was consistent with a diagnosis of PV, undefined CMPD and IMF
in 2, 2 and 1 cases, respectively, while it was non diagnostic in one case.
Conclusions. These results confirm the value of JAK2 mutational screening
to unravel occult CMPD and suggest a high prevalence of this genetic
aberration in patients with SVT.
1300
THE CALM INTERACTOR CATS, WHICH INFLUENCES THE SUBCELLULAR LOCALIZATION
OF THE LEUKEMOGENIC FUSION PROTEIN CALM/AF10 IS A MARKER FOR
PROLIFERATION
L. Fröhlich Archangelo, 1 E. Kremmer, 2 M. Hölzel, 2 D. Eick, 2 G. Przemeck,
2 M. Hrabé de Angelis, 2 A. Deshpande, 1 C. Buske, 1 S. Bohlander1 1 Med III Klinikum Grosshadern, MUNICH; 2 GSF, MUNICH, Germany
CATS is the CALM interacting protein expressed in thymus and
spleen. The CATS interaction region of CALM is contained in the leukemogenic
fusion protein CALM/AF10. CATS increase the nuclear localization
of CALM/AF10 and sequesters the fusion protein in the nucleolus.
The murine Cats is highly expressed during embryogenesis where
it is enriched in the CNS and expression decreases gradually while
embryos develop to later stages and is confined to thymus and ovary of
the adult organism. Cats is widely expressed in the hematopoietic compartment
and an striking up-regulation of Cats transcript was observed
in B220 + positive cells derived from a CALM/AF10 murine bone marrow
transplant model in comparison to the same population of a nonleukemic
mouse. We confirmed expression of endogenous CATS in
human thymus and show strong expression in leukemia, lymphoma
and tumor cell lines but not in non-proliferating T-cells. CATS expression
is regulated in a cell cycle dependent manner and is induced by
mitogens. The clear upregulation of CATS protein upon mitogenic activation
and its high expression in proliferating but not in quiescent cells
suggest a role of CATS in the control of cell proliferation. CATS-
CALM/AF10 interaction might thus play an important role in the
CALM/AF10-mediated leukemogenesis.
1301
R-FMD VS R-CHOP TREATMENT AS FIRST LINE THERAPY FOR FOLLICULAR LYMPHOMAS:
A SINGLE CENTER EXPERIENCE
M. Dell’Olio, C. Bodenizza, A.M. Carella, A. Falcone, M.M. Greco,
A. La Sala, S. Mantuano, L. Melillo, E. Merla, M. Nobile, G. Sanpaolo,
P. Scalzulli, N. Cascavilla
Casa Sollievo della Sofferenza Hosp, SAN GIOVANNI ROTONDO, Italy
Background. High response rates in follicular lymphoma (FL) with the
FMD protocol have been previously reported. The monoclonal anti-
CD20 antibody rituximab has been shown to induce a high response
rate in FL patients and to improve outcome when associated with classic
regimes (CVP or CHOP). Aims. We have evaluated the impact of R-
FMD as compared to R-CHOP as a first line therapy in patients with follicular
lymphomas, in terms of: complete response (CR), overall survival
(OS), feasibility, toxicity and the efficacy of PCR molecular analysis in
predicting clinical and molecular remission. Methods. Between September
2002 and June 2006, 40 pts with FL were enrolled in the study. Twenty
patients (M/F: 10/10, median age 54 years) received R-FMD treatment
in stage II-IV, FLIPI score: intermediate grade 10 pts, high grade 10
pts. R-FMD regimen was administered every 28 days for six cycles: Fludarabine
25 mg/m2 e.v. days 1-3, Mitoxantrone 10 mg/m2 day 1, Dexamethasone
20 mg days 1-3 and Rituximab 375 mg/m2 day 1.Granulocyte
colony-stimulating factor and Pneumocystis Carinii prophylaxis
was given. PCR molecular analysis was performed in 12 patients at diagnosis,
showing in 16 (80%) of them bcl-2 rearrangement. Twenty
patients (M/F: 8/12, median age 58 years) received R-CHOP treatment
in stage II-IV, FLIPI score: intermediate grade 8 pts, high grade 12 pts. The
CHOP regimen consisted of doxorubicin 50 mg/m2 on day 1, cyclophos-