ECLAP (European Collaboration on Low Dose Aspirin in Polycythaemia Vera) study
This study demonstrated that low-dose aspirin is safe in patients with PV, and most importantly that a treatment as simple as aspirin protects against blood clots such as strokes, heart attacks and deep vein thromboses. This study was performed throughout Europe and the UK and was published in New England Journal of Medicine in January 2005. Read the ECLAP study on aspirin in PV here:
NEJM May 2007: Efficacy and safety of low-dose aspirin in polycythemia vera
Reference: Landolfi New England Journal of Medicine 2005, volume 350 pages 111-124.

ECLAP study for vascular risk and risk of leukaemia in PV (Marchioli and Finazzi)
The ECLAP study demonstrates the importance of screening PV patients for vascular disease risk factors such as diabetes, smoking, cholesterol and family history of vascular disease. The study suggests that certain people may have a higher risk of developing leukaemia: patients over age 65 at diagnosis and those who use multiple drugs such as radioactive phosphorous and busulfan. This study implies that the risk of developing leukaemia from hydroxycarbamide is small. We cannot be certain of this, however, as most patients were followed up over a period of only three to four years. The study used data from the ECLAP trial. Read the ECLAP study for vascular and leukaemia risk in PV here:
Journal of Clinical Oncology April 2008: Vascular and Neoplastic risk in a large cohort of patients with polycythemia vera
Reference: Journal of Clinical Oncology 2005, Volume 23, Number 10, Pages 2224-2232.

Primary Thrombocythaemia (MRC-PT1) Trial
This trial compared various treatment alternatives for high-risk ET patients; the goal was to determine which treatment was most effective. The results were published in 2005. The trial compared treatment combining hydroxycarbamide and low-dose (75mg) aspirin versus anagrelide and low-dose aspirin. The trial studied ET patients at high risk of thrombosis. Patients were judged to be high-risk if they had at least one of the following factors:

1. Age over 60 years
2. Platelet levels higher than 1000 x 109/L
3. Previous thrombosis or haemorrhage
4. Treated hypertension
5. Diabetes

The authors concluded that hydroxyurea and aspirin should be first line therapy for most high-risk ET patients. Read the article about treating high-risk ET here: NEJM July 2005: Hydroxyurea compared with anagrelide in high-risk Essential Thrombocytosis
Reference: New England Journal of Medicine 2005,353;33-45.

Latest PT-1 Trial Publications

Three additional publications of note have emerged from the PT-1 trials. One study evaluated whether haematologists can predict a patient's risk of myelofibrois (MF) by reviewing samples of the patient's bone marrow. The study also sought to determine how difficult it is to apply the new WHO criteria for diagnosing ET. This study assessed bone marrow samples from the PT-1 trial. The results suggest that the WHO criteria are difficult to apply and do not predict thrombosis, haemorrhage, myelofibrosis or leukaemia. Interestingly, there has recently been a stimulating critique of the WHO criteria and a commentary from other authors regarding this debate. Read more about diagnosing MPDs using WHO criteria in these articles:

Blood Journal May 2007: Proposals and rationale for revision of the WHO diagnostic criteria for PV, ET and MF: recommendations from an ad hoc international expert panel
Reference: Blood First Edition Paper, prepublished online; doi 10.1182/blood-2007-04-083501.

Blood Journal April 2008: The revised WHO diagnostic criteria for PV, ET and MF: and alternative proposal
Reference: www.bloodjournal.org, prepublished online; doi 10.1182/blood-2007-12-128454.

Blood Journal May 2008: Pre-fibrotic myelofibrosis: is this diagnosis valid?
Reference: www.bloodjournal.org, prepublished online; doi 10.1182/blood-2007-10-114303.

Blood Journal May 2008: Bone marrow pathology in ET: interobserver reliability and utility for identifying disease subtypes
Reference: www.bloodjournal.org, prepublished online; doi 10.1182/blood-2007-05-091850.

The study also compared JAK2-positive patients and JAK2-negative patients. The results suggested that JAK2-positive patients were more likely to suffer from thrombosis, although other studies disagree. The JAK2-positive patients needed a lower dose of hydroxycarbamide (HC); and anagrelide offered these patients better protection than HC against arterial thrombosis. Read more about these questions:

Lancet 2005: Definition of subtypes of ET and relation to PV based on JAK2 V617F mutation status: a prospective study
Reference: www.thelancet.com, Volume 366, Dec 3, 2005

Lastly, a recent analysis of patients with MPL mutations in the study suggested that patients with these mutations have a lower haemoglobin and higher platelet counts at diagnosis, but do not have any difference for complications or survival. Read about MPL mutations here:
Blood May 2008: MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort
Reference: www.bloodjournal.org, doi: 10.1182/blood-2008-01-131664

Two arms of this study remain open and are set to answer very important questions. We want to understand the natural history of ET in young patients. We also want to determine whether patients aged between 40 and 60 years with no high-risk features would benefit from treatment with hydroxycarbamide. (High-risk patients for purposes of the study include those with platelets counts greater than 1500 x 109/L OR previous thrombosis or haemorrhage OR treated hypertension OR diabetes.) This study should answer important questions about long-term side effects of HC.

You can read the trial protocol and other information about this study on the trial website:
http://www.ctsu.ox.ac.uk/projects/leuk/pt1/

Pregnancy in PV
This study was presented in prestigious Presidential Free Communications at the British Society of Haematology Meeting in April 2005. It found that patients actively treated according to a protocol had much better chance of a successful pregnancy.
The management and outcome of 18 pregnancies in women with polycythemia vera

A guideline for the management of Polycythaemia/Erythrocytosis
A guideline for the management of erythrocytosis (a high haemoglobin or red cell number) has been prepared and published by a group of experts in the field under the auspices of the British Committee for Standards in Haematology and the British Society for Haematology. This group considered all the published evidence and formulated recommendations for classification, investigation and management of both Polycythaemia Vera and secondary erythrocytosis due to cardiac, respiratory and other causes. This document is important because it evaluates the available evidence and provides a framework and advice for management of individual patients. However, there is a lack of high quality evidence in much of this area. This is a major limitation of the guideline. In many areas there is either poor quality or no evidence and the group could only form an opinion using available information. There is therefore a great need for further clinical trial work to investigate best management of these patient groups.

You can read more here:
http://www.bcshguidelines.com/pdf/polycythaemia.pdf

Effect of therapy upon JAK2 levels
Two recent papers suggest that the level or amount of JAK2 can be affected by treatment. This is important as this reduction may have an impact on long-term consequences of disease. The goal is to prevent conversion to leukaemia or myelofibrosis. The first paper from Jones et al shows variable reduction in levels with Glivec but a hint of better effect with interferon alpha.

Blood Journal April 2005: Acute Leukaemia in PV

Blood Journal April 2006, Vol. 107, No. 8, Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha

The second paper comes from a collaborative study in France showing a progressive decline in JAK2 levels after treatment with a different formulation of interferon alpha (so-called PEGA-SYS) with on-going reductions even after 2 years. This study is likely to be followed by a much bigger study in the UK and across Europe and USA.

bloodjournal.org - Blood, 15 September 2006, Vol. 108, No. 6, High molecular response rate of PV patients treated with pegylated interferon alpha 2a