Myeloid & Lymphoid disorders in practice - 2007

Comment: Can one pill a day really keep cancer at bay?
John Reilly
pp 2-2
One morning last summer, despite being half asleep, caffeine-deficient and late, I could not help but notice the headline of the daily paper, ‘One pill a day keeps cancer at bay. Breathtaking new drug gives leukaemia patients a lifeline’. What struck me was not just the front-page coverage of a blood disease (imatinib [Glivec®, Novartis, UK] and chronic myeloid leukaemia [CML] if you had not guessed), but that the article was deemed worthy to rival news of Wayne Rooney’s fitness to join England’s World Cup squad. So what could have prompted such a high-profile feature on CML?
Dasatinib: a new therapy for myeloproliferative disorders
Richard E Clark
pp 3-5
In chronic myeloid leukaemia (CML), it is now clear that the tyrosine kinase BCR-ABL is central to the pathogenesis of early chronic phase disease. BCR-ABL arises from the t(9;22) Philadelphia translocation, and is an abnormal constitutively active form of the normal ABL kinase. Like SRC tyrosine kinases, ABL and BCR-ABL kinases toggle between inactive and active forms. Adenosine triphosphate (ATP) binds to the active form, and phosphate is transferred from ATP to a tyrosine residue on a target substrate.
Current treatment options in primary myelofibrosis
Giovanni Barosi
pp 6-8
The most frequent and clinically relevant treatment problems in primary myelofibrosis (PMF) are relief of anaemia and control of splenomegaly. Therapeutic options for relief of anaemia include danazol, recombinant human erythropoietin (rHuEPO) and low-dose thalidomide. Chemotherapeutic agents, radiation therapy, splenectomy and reduced-intensity conditioning (RIC) regimens followed by related or unrelated allogeneic stem cell transplantation (SCT) can be used to treat splenomegaly. Treatment of PMF remains merely palliative. Symptomatic therapy is indicated for patients with symptoms attributable to anaemia or related to splenomegaly, bleeding problems or life-threatening thrombocytopenia, portal hypertension and life-threatening gastrointestinal bleeding.
Antithrombotic agents in myeloproliferative disorders
Raffaele Landolfi and Tiziano Barbui
pp 9-10
Patients with chronic myeloproliferative disorders (MPDs) – particularly polycythaemia vera (PV) and essential thrombocythaemia (ET) – have an increased incidence of venous and arterial thrombotic events, which may represent the first clinical manifestation of the disease and even precede the diagnosis by several years. Treatment and prevention of vascular events often requires cytoreduction and the use of antithrombotic drugs. Most of these agents, however, have not been tested in this setting and, due to a tendency to cause bleeding and the uncertain pathogenesis of thrombophilia, require specific studies to assess their benefits and risks.
The importance of bone marrow pathology in CMPDs
Bridget S Wilkins
pp 11-13
Bone marrow histology, particularly when enhanced by immunohistochemistry, contributes significantly to the diagnosis of chronic myeloproliferative diseases (CMPDs). Clarification of the molecular basis of CMPDs is progressing rapidly and bone marrow histology might become less important as a result. Currently, however, it is still highly relevant in the clinical practice of most haematologists and haematopathologists. In the acute leukaemias and some other haemopoietic neoplasms, primacy is given to specific genetic abnormalities. As yet, an equivalent role for genetic information as the basis for diagnosis and prognosis has not become established for most CMPDs, with the exception of chronic myeloid leukaemia (CML).
EXELS: a new long-term observational study in ET
Claire N Harrison
pp 14-15
A key goal in the treatment of essential thrombocythaemia (ET) is to reduce patients’ long-term risk of experiencing disease-related complications while minimising those associated with therapy. Cytoreductive treatment options commonly used for managing ET have different mechanisms of action and present different clinical challenges relating to the risk of general bone marrow depression, other unwanted side-effects and potential transformation to a more aggressive disease such as acute myeloid leukaemia or myelofibrosis. In developing an optimal management plan for ET patients, it is, therefore, crucial to understand the long-term safety and efficacy of the available treatment options.