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

12 th Congress of the European Hematology Association
AMLMD/tAML 27, MDS/tMDS 18) who received 71 FLA cycles, (10
FLA, 61 FLA+Ida) in which unconjugated filgrastim (dosage: 300
mcg/sqm/day) was given from day 12 until neutrophils recovery
(>500/mmc); status before chemo: untreated 41 (57.7%), CR/PR 14
(19.7%), active disease 16 (22.6%). Hematological recovery was evaluated
only in pts with a documented response to treatment (complete
remission, CR, or partial remission, PR). Median values of CTC grade 4
neutropenia and thrombocytopenia duration in the two groups were
compared with the Mann Whitney U-test; cases of documented infections
and episodes of fever of unknown origin (FUO) were reported and
incidence in the two groups was compared with the chi-square test.
Table 1.
Results. full results are shown in the Table 1; in one case a second PEGfilgrastim
injection was administered at day 32 for delayed recovery. Conclusions.
our preliminary results suggest that a single PEG-filgrastim injection
after FLA regimens is equivalent to daily unconjugated filgastrim; in
fact, haematological recovery and incidence of infective/FUO episodes
during grade 4 neutropenia resulted comparable in the two groups of
pts. Confirmation in a larger population of pts is warranted. Moreover,
as the single dose is preferred by pts to daily injections, the overall costeffectiveness
of the PEG-filgrastim formulation could prove favourable.
1086
HYPEREOSINOPHILIC SYNDROMES (HESS)-CLINICAL PRESENTATION AND VARIABLE
RESPONSE TO TREATMENT-A CASE SERIES
S. Mitra, 1 P. Thornton, 2 P.T. Murphy3 1 Mater University Hospital, DUBLIN; 2 Connolly Hospital,Dublin 15,
DUBLIN, Ireland; 3 Beaumont Hospital, DUBLIN, Ireland
Background. Hypereosinophilic syndromes (HESs) refers to a heterogenous
group of disorders characterised by marked blood eosinophilia
(>1500/cu mm) and tissue eosinophilia (lasting for more than 6
months),in the absence of other eitiologies for eosinophilia, resulting in
end organ damage. Eosinophilias may be a reactive condition or due to
a chronic myeloprolifer- ative disorder( with evidence of clonal proliferation).Reactive
eosino- philias are due to release of cytokines(IL-3,IL-
5,GM-CSF etc) and the common causes are parasitic infections, allergic
diseases, vasculitides, drug reactions and malignancies .Clonal
eosinophilias are those in which the eosinophilia is a part of a clonal
haema- tological malignancy, which is very often associated with the
fusion gene FIP1L1-PDGFR α which causes the generation of a constitutively
active Tyrosine Kinase.Several visceral complications like cardiomyopathies,
nervous system involvement (eg paraparesis, cerebral
infarction, eosinophilic meningitis etc) are often fatal illnesses. Treatment
modalities for HES includes corticosteroids, chemotherapeutic
agents (hydroxyurea cyclophosphamide , vincristine) and α-interferon.
Newer treatment modalities including tyrosine kinase inhibitors (eg Imatinib
mesylate) and monoclonal anti-IL5 antibodies are now available.
Patients carrying this fusion gene respond well to the Tyrosine Kinase
Inhibitor,Imatinib. Some patients with HES,that are negative for this
fusion gene may also respond to Imatinib, suggesting that in such cases
other Tyrosine Kinases may be dysregulated. Aims. Retrospective
review of the variable response of 7 patients with HES (over a period of
6 months),to current treatment modalities. Methods.The 7 patients (6
Male, 1 Female; age range 37-80 yrs; mean age 56 yr) presented with
eosinophilia in the range 2600-73,000 /cu mm. A response to treatment
was defined as Eosinophil count80 yr) was treated with Hydroxyurea initially.
Table 1. HES-Patient Characteristics.
Results. Four of the six patients receiving Imatinib responded to it. Of
the 2 patients not responding to Imatinib,1 responded par- tially to
Hydroxyurea and the other did not respond to monotherapy with
steroid or α-interferon (but eventually responded to a combination of the
two). The patient who had initial treatment with Hydroxyurea responded
well. Of the 7 patients 1 was positive for the FIP1L1-PDGFRa fusion
gene,1 result was equivocal, 3 were negative and 2 were not tested. Of
the 2 that were negative 1 responded to Imatinib. Conclusions. Thus
response of HES patients to the various treatment modalities, is variable
and often unpredictable. A trial of Imatinib is worthwhile in all
cases,including the FIP1 negative cases.
1087
CHOICE OF ENDOTHELIAL MARKER IS CRUCIAL FOR QUANTIFICATION OF BONE
MARROW MICROVESSEL DENSITY IN CHRONIC LYMPHOCYTIC LEUKEMIA
L. Smolej, P. Kasparova, D. Belada, P. Zak
University Hospital and Medical School, HRADEC KRALOVE, Czech
Republic
Introduction. Angiogenesis is a potential prognostic factor in chronic
lymphocytic leukemia (CLL). Elevated levels of angiogenic factors have
been found in peripheral blood of CLL patients. However, results of
studies assessing bone marrow neovascularization in CLL are controversial,
in part due to different antibodies used for immunohistochemical
identification of endothelial cells and different methods of assessing
microvessel density (MVD). Moreover, there are insufficient data regarding
relationship of marrow angiogenesis to prognostic markers in CLL
such as clinical stage, pattern of marrow infiltration, genetic abnormalities
detected by FISH, or mutation status of immunoglobulin heavychain
variable-region genes (IgVH). Aims. 1. To quantify MVD in bone
marrow biopsies from CLL patients and control group using two different
monoclonal antibodies and reproducible method of vessel counting;
2. To assess relationship of MVD to most important prognostic factors.
Methods. We analyzed MVD in bone marrow biopsies from untreated
patients with CLL using immunohistochemical staining of endothelial
cells with monoclonal antibodies against CD34 (n=22) and von Willebrand
factor (vWF, n=18). Control group consisted of 17 biopsies from
age- and sex-matched individuals without evidence of malignancy in
bone marrow. Microvessel density was assessed under light microscope
equipped with image analysis software and calculated using hot spot
method, i.e. identification of three loci with highest accumulation of
microvessels under low (100x) magnification and counting microvessels
in three high-power fields (400x) per hot spot. MVD was expressed
as mean number of microvessels per mm2 . CLL cohort was further subdivided
according to clinical course (stable vs. progressive), Rai stage (0
vs. I-IV), pattern of marrow infiltration (non-diffuse vs. diffuse), genetic
abnormalities (favourable, i.e. no abnormality or del13q14 as a sole
aberration vs. unfavourable, i.e. del 17p / del11q / +12), and IgVH mutation
status (mutated vs. unmutated). Results. MVD was significantly elevated
in CLL group in comparison to controls using either antibody
(CD34, mean±standard deviation [SD], 75.6±50.6, 95% confidence interval
of mean [CI], 53.2-98.1 vessels/mm2 vs. 47.4±21.8, 95% CI, 36.2-58.6
vessels/mm2 , p=0.039; vWF, 21.3±16.5 vessels/mm2 , 95% CI, 13.1-29.5
vs. 11.5±8.5, 95% CI, 6.8-16.2 vessels/mm2 , p=0.017). However, no sig-