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

Myeloproliferative disorders - Clinical
0637
PULMONARY HYPERTENSION IN ESSENTIAL THROMBOCYTHEMIA
A. Altintas, 1 T. Boyraz, 2 S. Pasa, 1 T. Cil, 1 M.A. Kaplan, 2 O. Ayyildiz 1
1 Dicle University Medical Faculty, DIYARBAKIR; 2 Dicle University, Medical
Faculty, DIYARBAKIR, Turkey
Increased incidence of pulmonary hypertension (PH) has been reported
in patients with chronic myeloproliferative disorders (MPDs). However,
the exact incidence of PH in essential thrombocythemia (ET) is
unknown and most of the reported literature consists of case reports or
small studies. Previously or newly diagnosed 46 patients with ET and 40
patients with reactive thrombocytosis secondary to iron deficiency anemia
were eligible for this study in between January 2004 to February
2007. Diagnosis of PH was established if right ventricular systolic pressure
> 35 mmHg by transthoracic echocardiography. Diagnosis of PH
was established in 22 (47.8%) of 46 patients with ET. Seven patients
with PH were newly diagnosed ET. Five patients with PH were in low,
and the other patients with PH were in intermediate or high risk category.
However, none of the patients with reactive thrombocytosis with
iron deficiency anemia had PH. In conclusion, PH appears to be common
in patients with previously or newly diagnosed ET. All patients with ET
should be evaluated for development of PH at the time of diagnosis and
during their follow-up period. Larger and prospective designed studies
are needed to clarify the long-term impact of PH on the survival of these
patients. It should illuminated whether cytoreductive treatment and use
of aspirin prevent development of PH, and their effects on progress of
PH and prognosis. In addition, especially in low risk group patients who
are not recommended treatment but aspirin the role of PH on prognosis
should be determined.
0638
SERUM VEGF LEVELS ARE RELATED WITH METALLOPROTEINASE-9 (MMP-9) LEVELS IN
PATIENTS WITH POLYCYTHAEMIA VERA
S. Theodoridou, 1 T. Vyzantiadis, 2 I. Venizelos, 1 S. Vakalopoulou, 1
V. Perifanis, 1 E. Mandala, 1 E. Leukou, 1 I. Klonizakis, 1 V. Garypidou1 1 Hippokration Hospital, THESSALONIKI; 2 Aristotle University1st Microbiology
Dep, THESSALONIKI, Greece
The release of angiogenic factors by physiological stress or malignant
cells is known to mobilize hematopoiesis. The mechanism by which
these factors recruit stem cells is unknown. It has been shown that VEGF
(vascular endothelial growth factor) and PlGF (placenta growth factor)
promote hematopoiesis through the up regulation of MMP-9 (metalloproteinase
9) levels. MMP-9 induces the cycling of Go hematopoietic
stem cells. In polycythemia vera (PV) there is evidence of increased
angiogenesis and several angiogenic factors and microvessel density of
the bone marrow have been examined and found increased. However
the aetiology of the bone marrow hyperplasia is unidentified. We tried
to investigate the role of the two angiogenic factors (VEGF and MMP-
9) that are known to synergize and regulate hematopoiesis, in PV
patients. A total of 38 patients with PV (mean age 56,1±2,5 years) were
included. ∆wenty five patients were managed with phlebotomy, four
received hydroxyurea, eight were managed with hydroxyurea and phlebotoby
and one was treated with interferon. Three had clinically detected
spleen enlargement. The control group consisted of 22 healthy subjects
(mean age 55,3±1,3 years). Serum VEGF levels were found increased
in PV patients in comparison to control group (510,6±87,8 pg/mL vs
182,7±27,2 pg/mL respectively, p=0,032). Although serum MMP-9 concentrations
did not differ among polycythaemic patients and the control
group (316±40,4 pg/mL and 446,2±72,6 pg/mL, respectively, p=0,086) we
found a statistically significant positive correlation in the patients group
between serum MMP-9 levels and VEGF levels (r=0,36, p=0,03). VEGF
plays a prominent role as an angiogenesis inducer and was found very
significantly increased in the group of polycythaemic patients. The role
of MMP-9 in angiogenesis and hematopoietic cell stimulation is well
established. It has been shown that MMP-9 has the capacity to generate
sKitL from membrane bound KitL and mobilizes stem cells. The positive
correlation (although slight) of VEGF and MMP-9 serum levels in
PV patients may reflect the autocrine signaling pathways that exist
between the two factors in the bone marrow microenviroment. The
role of angiogenic factors is under investigation in PV and myeloproliferative
syndromes and further studies are needed to determine their role
in the pathogenesis of these disorders.
12 th Congress of the European Hematology Association
0639
IS RED CELL MASS DEFINITELY USELESS TO CLASSIFY MYELOPROLIFERATIVE
DISORDERS IN THE JAK2 ERA?
Chr. Laguillier, 1 V. De Beco, 1 B. Cassinat, 2 S. Burcheri, 1
P. Weinmann, 1 P. Fenaux, 1 J.J. Kiladjian1 1 2 APHP, Hopital Avicenne, BOBIGNY; APHP, Hopital Saint-Louis, PARIS,
France
Background. Since the discovery of JAK2V617F mutation, new algorithms
to diagnose and classify MPD are still debated. The current WHO
criteria for PV require either an elevated RCM above 125% of predicted
value, or Hb level above 18.5 g in men and 16.5 g in women. Some
investigators recently proposed to set the threshold for Hematocrit (Ht)
at 52% in men and 48% in women to diagnose PV in JAK2V617F
patients (Green & Campbell, NEJM, 2006). RCM analysis could therefore
become obsolete in JAKV617F patients, if one considers that mutated
PV and ET are almost similar conditions. However, no prospective
clinical data support this plausible assumption, and distinguishing PV
from ET still seems necessary, at least until those hypotheses are validated.
Aims. To assess the diagnostic value of RCM measurement in the
diagnosis of PV in patients with Hb or Ht below values used in currently
validated or proposed criteria. Methods. We reviewed all RCM measurements
performed in patients suspected of MPD in a single nuclear
medicine laboratory during a one-year period. Results. 66 patients were
referred for RCM measurement between January 05 and March 06.
Among them, 19 had isolated thrombocytosis, i.e. both Hb below WHO,
and Ht below Greens’ proposed criteria, respectively. JAK2V617F mutation
was found in 10 pts, while 9 pts had wild-type (wt) JAK2. RCM was
below 125% of predicted value in all the 9 wt-JAK2 pts. Among the 10
patients with JAKV617F, 7 had measured RCM above and 3 below 125%
of the predicted value, respectively. Therefore, 7/19 (37%) patients presenting
with isolated thrombocytosis had PV based on RCM measurement,
but they would have been diagnosed as ET based on Hb or Ht values
only. All those patients had JAK2V617F mutation, while all wt-JAK2
ET had normal RCM. Conclusions. In this series of unselected consecutive
patients with isolated thrombocytosis referred for RCM determination,
we found that 37% of cases would have been misdiagnosed as ET
instead of PV in the absence of RCM measurement, this proportion
reaching 70% in the group of JAKV617F patients. Those results suggest
that RCM should be performed in JAK2V617F patients with isolated
thrombocytosis, for proper MPD classification and management. On
the other hand, RCM is useless in wt-JAK2, as PV is extremely rare in
such patients.
0640
IMATINIB AT 100MG ONCE WEEKLY IS SUFFICIENT TO MAINTAIN HAEMATOLOGIC AND
MOLECULAR REMISSION IN PATIENTS WITH IDIOPATHIC HYPEREOSINOPHILIC
SYNDROME
G. Helbig, 1 B. Stella-Holowiecka, 1 S. Grosicki, 1 J. Wojnar, 1
M. Wieczorek, 2 G. Bober, 1 M. Krawczyk, 1 J. Holowiecki1 1 2 Silesian Medical University, KATOWICE; Department of Paediatric Haematology,
CHORZOW, Poland
Background. Persistent blood eosinohilia is usually associated with a
large number of clonal and non-clonal disorders. Idiopathic hypereosinophilic
syndrome (HES) is a condition of unknown cause with overproduction
of eosinophils resulting in organ damage. In a small subset
of patients (pts) previously regarded as having HES, the disease is caused
by the FIP1L1-PDGFRA fusion tyrosine kinase. In these pts the tyrosine
kinase blocker- imatinib is highly effective inducing a haematologic and
molecular remission. Some pts lacking this transcript can also benefit
from imatinib. Of crucial importance is to define the policy of long term
treatment and this issue is adressed in this report. Material and methods.
21 pts affected by HES were studied for FIP1L1-PDGFRA by RT-PCR and
this fusion was detectable in 2 pts (9%). 10 out of 21 pts were treated
with imatinib at 100 to 300 mg daily, because of advanced organ damage
and/or marked hypereosinophilia. The dose was reduced to 100mg
once weekly after a complete haematologic remission (CHR) was
achieved. Results. Median age at diagnosis was 54 years (range 6-67 yrs)
with male/female ratio 1.5/1. Heart and spleen were most frequent
involved. Cytogenetics was obtained in 7 out of 10 pts and it was normal.
Median number of prior lines of therapy was 3 (range 1-8). Median
time from diagnosis to imatinib was 55 months (range 6-145). Troponin
level was not increased before imatinib commencement. 3 pts, all
male, showed rapid response to imatinib at 100 mg daily. In 2 FIP1L1-
PDGFRA positive pts, CHR was achieved after 14 and 67 days respec-
haematologica/the hematology journal | 2007; 92(s1) | 239