ALBERTO ALVAREZ (BARCELONA)
ESSENTIAL THROMBOCYTHEMIA
Hematology Department, Hospital Clínic de Barcelona, Spain
There is a general consensus to adopt a risk-adapted treatment strategy to personalize the
indication of treatment by the vascular risk in essential thrombocythemia (ET). According to
classical risk stratification, patients younger than 60 years without history of thrombosis and
with platelet count below 1,500 × 109/L are considered at “low-risk” for thrombotic and
bleeding events and do not require myelosuppression whereas cytoreductive agents are
recommended in those patients presenting any of these risk factors. However, the annual rate
of thrombosis in low-risk ET patients treated according to classical stratification remains
higher than in non-MPN population, suggesting the possibility to achieve a better therapy
classification.
A new scoring system to predict thrombosis was recently developed, based on age > 60 years,
thrombosis history, cardiovascular risk factors and JAK2V617F mutation. Three risk groups
were identified, with the corresponding annual rate of thrombosis for low-, intermediate- and
high-risk patients being 1.19%, 2.26%, and 4.88%, respectively. A re-analysis of the original
IPSET-thrombosis data showed a remarkable lower rate of thrombosis in conventional low-risk
category without JAK2 mutation, especially if cardiovascular (CV) risk factors were absent
(0.44% pts/yr versus 1.05% pts/yr for those with CV risk factors). In addition, a subgroup of
patients classified as low risk according to the classical stratification but presenting CV risk
factors and a JAK2 mutation showed a thrombosis rate of 2.57%. Retrospective studies
showed that low-dose aspirin was unable to reduce the risk of thrombosis observed in
conventional low risk patients with both JAK2-positive and CV risk factors suggesting the need
for a more intensive primary prophylaxis in this subset of patients. However, the only
randomized clinical trial performed on intermediate risk ET did not observe a benefit of adding
hydroxyurea to antiplatelet therapy and reported a low rate of thrombosis (0.94% pts/year)
in the whole cohort of intermediate risk patients.
More recently, a genomic classification for MPN has been proposed based on the results
obtained by next generation sequencing and includes eight molecular groups with specific
prognostic implications. 1. MPN with TP53 disruption/aneuploidy: affecting <2% of ET patients
was associated with acute myeloid leukemia and shorter survival. 2. MPN with
spliceosome/chromatin mutations: 8% of ET patients, associated with myelofibrotic
transformation. 3. MPN with CALR mutation: 20% of ET patients, lower rate of thrombosis. 4.
MPN with MPL mutation: <5% of ET. 5. MPN with homozygous JAK2 mutation: 5% of ET
patients, higher risk of myelofibrosis. 6. MPN with heterozygous JAK2 mutation: 45% of ET
patients, low rate of disease progression. 7. MPN with other driver mutation: <2% of ET
patients. 8. MPN with no known driver mutation: 10% of ET patients and usually associated
with benign outcome.
In summary, conventional risk classification constitutes the basis for identifying high risk
patients and deciding on cytoreduction need. The addition of cardiovascular risk factors and
JAK2 mutational status is useful for refining thrombotic risk in conventional low risk patients.
Finally, the integration of genomic data with clinical variables might improve the prediction of
patient’s outcomes helping clinicians to treatment decisions.
SCIENTIFIC PROGRAMME
SESSION I
OPTIMIZING
CYTOREDUCTION
SESSION II
MANAGEMENT OF CML
WITH TKI
SESSION III
MPN RISK
STRATIFICATION
INCLUDING VASCULAR
EVENTS
DEBATE 1
INTERFERON ALPHA
SHOULD BE FRONT LINE
THERAPY IN ALL ET/PV
PATIENTS
ROUNDTABLE 1
INFECTIONS IN
MYELOPROLIFERATIVE
DISORDERS, INCLUDING
CML
ROUNDTABLE 2
PREGNANCY AND
PARENTING
DEBATE 2
ALLOGENEIC STEM CELL
TRANSPLANTATION
SHOULD BE CONSIDERED
THIRD LINE OPTION IN
CHRONIC PHASE CML
SESSION IV
EVOLVING THERAPIES
IN MYELOFIBROSIS
SESSION V
MANAGEMENT OF
ADVANCED AND UNUSUAL
DISEASE (MPN AND CML)
SESSION VI
TREATMENT FREE
REMISSION IN CML
KEYNOTE LECTURE
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FO R A POSTER
PRESENTATION
DISCLOSURES