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

gene fusion is an independent prognostic factor in ALL patients. Identification
of this genetic entity in adult ALL at diagnosis is crucial for
understanding the nature of adult acute lymphoblastic leukaemia and for
deciding optimal treatment
Figure 1. Differences in overall survival of Ph + ALL and Ph – .
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CHRONIC EOSINOPHILIC LEUKAEMIA (ASSOCIATED WITH FIP1L1-PDGFRA)-DRAMATIC
RESPONSE TO IMATINIB MESYLATE
S. Mitra, 1 D. Thornton2 1 2 Mater University Hospital, DUBLIN; Connolly Hospital, Dublin 15,
DUBLIN, Ireland
Background. Chronic Eosinophilic Leukaemia (CEL) is a myeloproliferative
disorder in which an autonomous clonal proliferation of
eosinophilic precursors, results in persistently increased numbers of
eosinophils in the blood, bone marrow and peripheral tissues. Organ
damage occurs as a result of leukaemic infiltration or due to the release
of cytokines and enzymes by eosinophils. CEL along with idiopathic
hypereosinophilic syndrome constitute the Hypereosinophilic syndromes
(HESs). The recent WHO classification criteria for diagnosis of
HES exclude patients with underlying infections, allergic, autoimmune,
pulmonary or clonal lymphoid and non myeloid disorders that are
known to be associated with secondary eosinophilia in addition to
myeloproliferative or myelodysplastic disorders that could give rise to
clonal eosinophils. CEL is caused by autonomous proliferation of clonal
eosinophilic precursors, whereas idiopathic HES is diagnosed when
the criteria for CEL are met but there is no evidence of clonality or neoplastic
myeloid cell proliferation. Based on the WHO diagnostic criteria,
cases of HES found to be associated with a clonal chromosomal deletion
that gives rise to FIP1L1-PDGFRA fusion gene should be reclassified as
CEL. Case report. We report a 39 year old man who presented with complains
of headaches, left earache, rinorrhea, pyrexia and increased sweating.He
had a background history of seasonal rhinitis. On examination his
left tympanic membrane appeared inflamed.He had no evidence of
peripheral lymphadenopathy or splenomegaly. His FBC revealed Hb
13.9, WCC 78.1, Neut 9.6 ,Eosinophils 55.1 and Plat 183. Blood film
revealed polychromasia, nucleated RBCs, marked eosinophilia and left
shifted neutrophil maturation. Bone marrow- hypercellular marrow with
prominent granulopoiesis overwhelmingly along the eosinophilic maturation
(85% of the nucleated elements).Cytogeneics-46XX,no abnormal
clone detected.CT-Splenomegaly 14 cm.He was commenced on oral
Prednisolone.Following 2 weeks of steroids there was no response.
Hence Imatinib was commenced and Prednisolone was tapered off. In
1 week’s time his eosinophil count was down to 0.4 .His Peripheral
blood came back as positive for the FIP1L1-PDGFRA mutation (by single
step RT-PCR analysis) Three months after being on Imatinib 100mg
once daily, his peripheral blood was negative for the FIP1L1-PDGFRA
mRNA( by nested RT PCR), indicating a complete molecular response.
After one year of follow up,he is in complete haematological and molecular
remission of chronic Eosinophilic leukaemia. Discussion. Before the
1990s, lack of evidence for a reactive cause of hypereosinophilia or
chronic eosinophilic leukemia (e.g. presence of a clonal cytogenetic
12 th Congress of the European Hematology Association
abnormality or increased blood or bone marrow blasts) resulted in diagnosticians
characterizing such nebulous cases as idiopathic hypereosinophilic
syndrome (HES). However, over the last decade, significant advances in
our understanding of the molecular pathophysiology of eosinophilic disorders
have shifted an increasing proportion of cases from this idiopathic
HES pool to genetically defined eosinophilic diseases with recurrent
molecular abnormalities. The majority of these genetic lesions result in
constitutively activated fusion tyrosine kinases, the phenotypic consequence
of which is an eosinophilia-associated myeloid disorder. Most
notable among these is the recent discovery of the cryptic FIP1L1-
PDGFRA gene fusion in karyotypically normal patients with systemic
mast cell disease with eosinophilia or idiopathic HES, redefining these
diseases as clonal eosinophilias. A unique interstitial deletion on chromosome
4q12 leads to expression of the FIP1L1-PDGFRα fusion tyrosine
kinase. Rearrangements involving PDGFRA and PDGFRB in eosinophilic
chronic myeloproliferative disorders, and of fibroblast growth factor
receptor 1 (FGFR1) in the 8p11 stem cell myeloproliferative syndrome
constitute additional examples of specific genetic alterations linked to
clonal eosinophilia. The identification of populations of aberrant T-lymphocytes
secreting eosinophilopoietic cytokines such as interleukin-5
establish a pathophysiologic basis for cases of lymphocyte-mediated
hypereosinophilia. This recent revival in understanding the biologic basis
of eosinophilic disorders has permitted more genetic specificity in the
classification of these diseases, and has translated into successful therapeutic
approaches with targeted agents such as imatinib mesylate and
recombinant anti-IL-5 antibody. Conclusions. Imatinib, the Tyrosine
Kinase Inhibitor specific to Bcr-abl, Kit and PDGFR is an appropriate
therapeutic option for CEL with the FLIP1 like 1-PDGFR α. Fusion Gene
and often causes dramatic lowering of the eosinophil count.
Figure 1. Chronic Eosinophilic leukaemia (Bone Marrow).
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DIAGNOSTIC DIFFICULTIES IN IMPORTED LEISHMANIASIS IN ROMANIA
M.L.A. Balea, 1 M. Guran, 1 M.I. Balea, 2 A. Razvan1 1 2 Colentina Clonical Hospital, BUCHAREST; NIP Prof. Dr. Marius Nasta,
BUCHAREST, Romania
The extremely-polymorphous symptoms and signs of visceral Leishmaniasis
allow us to state that this infection is part of a grate imitators
group together with collagen diseases, systemic vasculitis-polyarteritis,
tuberculosis and HIV infection. With no occurrence before 1989, after the
liberation of the Romanian frontiers, no less than five visceral Leishmaniasis
have we diagnosed only in our clinic: three males and two females
ages 24-47. Four of the subject had come from Southern Greece and one
of subjects from Southern Italy (Reggio Calabria). The associated symptoms
and signs were as follows: prolonged-fever syndrome, consumption
syndrome, progressive hepatosplenomegaly, progressive adenomegaly,
progressive-aggravating pancytopenia and inflammatory
humoral syndrome accompanied by polyclonal hypergammaglobulinemia.
The subjects came at our clinic after 8-14 months of suffering, meanwhile
having been diagnosed by various medical-attendance unites with
the following hypothetic diagnoses: subacute bacterial endocarditis,
hepatic cirrhosis HVB + with hypersplenism and pancytopenia, idiopathic
thrombocytopenic purpura, neoplastic disorders, visceral toxoplas-
haematologica/the hematology journal | 2007; 92(s1) | 527