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

12 th Congress of the European Hematology Association
between F1+2 and TFPI and between TAT and TFPI. These data suggest
that macrovascular activation is platelet coagulant-associated and confirm
that microvascular activation is platelet-associated. ANA may have
antiplatelet and anticoagulant properties and hence may globally prevent
the thrombotic risk in ET.
1235
IMPACT OF JAK 2 MUTATION STATUS ON RESPONSE TO THERAPY IN PATIENTS WITH
ESSENTIAL THROMBOCYTHAEMIA
B. Padate, J.G. Smith
The Frimley Park Hospital, CAMBERLEY, United Kingdom
Background. The human myeloproliferative disorders (MPDs) are clonal
diseases originating from transformation of multipotent haemopoietic
stem cells. Until 2005, the molecular pathogenesis was obscure. The
recent discovery of the JAK2 V617F mutation in these disorders may
explain the clonal expansion of MPD cells. Current concept is that there
are 2 separate diseases, JAK2 mutated (+) and JAK2 wild type ( – ). Essential
Thrombocythaemia (ET), Polycythaemia Rubra Vera (PRV) and
Myelofibrosis are entities within a spectrum of mutated disorders where
duplication of mutant JAK2 allele with loss of the normal allele may
cause disease progression. Thus, the JAK2 mutation has brought a new
approach to the diagnosis, classification and potentially treatment of
MPDs. Aim. In the present study, the impact of JAK2 status on response
to the therapy, in patients with ET is evaluated. Methods. A group of 32
patients with Essential Thrombocythaemia (JAK2 + n=14: JAK2- n=18)
were studied. Response to therapy was retrospectively assessed and
compared with JAK2 + /- status. Other variables studied included platelet
count at the time of presentation, time required to achieve appreciable
response and the number of times that therapy was changed to achieve
that response. A platelet count of < 500×109 /L was taken as an appreciable
response to therapy. Results. out of 14 JAK2 + patients, two responded
poorly to first line therapy compared to 5 out of 18 JAK2' patients.
Interestingly most JAK2- poor responders were either resistant to
hydroxycarbamide or required higher doses of hydroxycarbamide to
control the counts. This led to the development of side effects and
requirement for change over of therapies. However, from the JAK2 – subgroup
8 patients responded well to anagrelide, 2 patients to busalphan,
3 to hydroxycarbamide and 1 patient to interferon alfa. From JAK2+
subgroup 1 patient responded well to anagrelide, 6 to hydroxycarbamide,
4 to busalphan and 1 to interferon alfa. On an average, more
patients from JAK2- subgroup required change in therapies to achieve
the appreciable response compared to patients from JAK2 + subgroup. In
patients with good response, the time required to achieve an appreciable
response by a particular therapy was not different in JAK2 – and JAK2 +
patients. Conclusions. On the basis of this small pilot study, we conclude
that ET patients with the JAK2 mutation are more responsive to current
first line therapies compared to JAK2- patients. Hence, JAK2 status may
inform therapeutic choice in myeloproliferative disorders in the future.
A large multi-centre prospective study is required to confirm the above
findings.
1236
HEMOPHAGOCYTIC SYNDROME AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION:
A PROSPECTIVE STUDY
A. Abdelkefi, 1 L. Torjman, 1 S. Ladeb, 2 A. Lakhal, 1 T. Ben Othman1 1 Centre National de Greffe de Moelle Osse, TUNIS, Tunisia; 2 Centre National
de Greffe de Moelle Oss, TUNIS, Tunisia
Background. Hemophagocytic syndrome is a histiocytic disorder characterised
by the activation and proliferation of benign macrophages with
hemophagocytosis throughout the reticuloendothelial system. Hemophagocytic
syndrome may be categorised into primary (or familial) and
secondary forms. This syndrome may be secondary to malignancy,
infection or autoimmune disease, and mechanisms involved are poorly
understood. Hemophagocytic syndrome is rarely reported after
hematopoietic stem cell transplantation. Aims. This prospective study
was conducted to evaluate the incidence of hemophagocytic syndrome
after hematopoietic stem cell transplantation (HSCT). Methods. Between
August 2006 and February 2007, all patients who received a hematopoietic
stem cell transplantation, were included in this prospective study,
at the National Centre for Bone Marrow Transplantation (Tunisia). All
the following criteria were needed for the diagnosis of hemophagocytic
syndrome: 1) sustained fever over 7 days 2) cytopenia (neutropenia
and/or thrombocytopenia) 3) presence of more than 3% mature
450 | haematologica/the hematology journal | 2007; 92(s1)
macrophages in bone marrow 4) hyperferritinaemia (> 1000 ng/mL)
Results. During this study, 79 patients (42 male, 37 female) received a
hematopoietic stem cell transplantation (34 allogeneic, 45 autologous).
In allogeneic HSCT recipients, we observed 4 cases of hemophagocytic
syndrome (4/34; 11.7%): 1 case of EBV-related hemophagocytic syndrome,
and 3 cases with no evidence of bacterial, fungal or viral infections.
Two patients died (including EBV-related hemophagocytic syndrome)
despite aggressive supportive care. In autologous HSCT recipients,
we observed only 1 case of CMV-related HS (1/45; 2.2%). This
patient is alive 3 months after transplant. Conclusions. This prospective
study provides a relatively high incidence of hemophagocytic syndrome
after allogeneic HSCT. When sustained fever with progressive cytopenia
and hyperferritinaemia are observed, hemophagocytic syndrome
should be suspected, and bone marrow aspirate considered. The rapid
diagnosis of hemophagocytic syndrome and the early initiation of an
appropriate treatment is essential for patient management.
1237
A ROLE FOR HLA-G IN CHRONIC LYMPHOCYTIC LEUKEMIA: FIRST RESULTS OF AN
ONGOING STUDY
A. Akyol Erikci, B.K. Karagoz, O.B. Bilgi, A.O. Ozturk
GATA Haydarpasa Training Hospital, ISTANBUL, Turkey
Background. Chronic lymphocytic leukemia (CLL), which is the most
common form of adult leukemia, is a new focus for researchers. Classically
used classification systems Binet and Rai do not supply enough
information about the prognosis of the disease. For this reason,
researchers started to investigate new prognostic markers for CLL. A
number of clinical and biological factors of prognostic relevance have
been identified. These include clinical characteristics such as age, gender
and performance status, and laboratory parameters like lymphocyte
count, bone marrow infiltration or LDH increase. Recently, new
prognostic parameters have been identified: serum markers such as,
sCD23, ß-2 microglobulin or thymidine kinase and genetic markers;
such as, gene abnormalities, the mutation status of IgVH genes or
markers for these factors such as CD 38 and ZAP 70. Aims. In our
study, we investigated the effect of HLA-G - which is first detected in
early placental trophoblasts -,ZAP-70, CD38, IL-10 on the prognosis of
CLL. HLA-G, molecule has limited tissue distribution and exerts multiple
immunoregulatory functions. Recent studies indicate an ectopic
up-regulation in tumor cells that may favor their escape from antitumor
immune responses. Methods. These parameters were studied
retrospectively in circulating B-CLL cells from 20 patients by flow
cytometry and IL-10 was studied by Elisa. Results. The proportion of
leukemic cells expressing HLA-G varied from 1% to 34%. Patients
over 12%, HLA-G positive cells (according to receiver operating characteristics
[ROC] analyses) had correlation with progression free survival
(p=0,045). We also detected a statistically significant difference
between Binet stage A; B and C (p=0,046). We also detected a positive
correlation between IL-10 and HLA-G (p30%), by flow cytometry and
FISH. They were assigned as typical or atypical according to the wellknown
6 antigen scoring system proposed initially by D. Catovsky et al.
(1994) and later improved by the addition of CD79b (1997). The following
cytogenetic anomalies were sought in all patients: t(11;14), 17p-,
11q-, +12, t(14q32), 13q-. Results. Scores 0-4, prevailed in MCL, in the
diagnostic groups of atypical B-CLL with 17p-, 11q-, +12 and in t(14q32)
lymphoproliferative disorder. The novel discriminant function (DF) pro-