NcXHF

JEAN-JACQUES KILADJIAN
Scores predicting overall survival in PV and ET also are
available; however, considering the long survival of these patients,
they currently are not used for therapeutic choices. 9,10
In contrast, in PMF, the overall median survival being is 6
years, and the relevant endpoint for prognostication is survival.
The International Prognostic Scoring System (IPSS) 11
is used at diagnosis to distinguish four risk categories (low,
intermediate 1, intermediate 2, and high risks). This system
has been refıned further by the development of the dynamic
IPSS (DIPSS), 12 which may be used at any time during
follow-up periods, and the DIPSS-plus score, 13 which incorporates
thrombocytopenia, transfusion requirements, and
cytogenetics. The role of CALR 14,15 and other mutations (i.e.,
EZH2, ASXL1, SRSF2, IDH1/2 mutations), which comprise a
high molecular risk category in PMF, 16 has been underscored
but has yet to be incorporated in a new prognostic model.
KEY POINTS
Therapy for myeloproliferative neoplasms currently is
based on the risk for vascular complications (thrombosis
and hemorrhage) and requires a strict control of other
well-known cardiovascular risk factors (e.g., smoking,
hypertension, diabetes, dyslipidemia).
Phlebotomy to maintain the hematocrit less than 45% and
low-dose aspirin are the cornerstone of therapy for
polycythemia vera, although patients older than age 60 or
who have a history of thrombosis (i.e., high-risk patients)
should receive a cytoreductive agent.
First-line therapy for high-risk polycythemia vera includes
hydroxyurea or interferon alfa, whereas ruxolitinib has
been approved recently for patients whose disease is
resistant to or who are intolerant to hydroxyurea.
Patients with essential thrombocythemia may receive low-dose
aspirin plus hydroxyurea when they are at high risk.
Anagrelide often is preferred as second-line therapy, whereas
interferon alfa also may be useful in subgroups of patients.
Treatment of myelofibrosis is often symptom driven, and
ruxolitinib currently is the treatment of choice in patients
with intermediate- or high-risk disease who have
symptomatic splenomegaly and disabling symptoms.
TREATMENT OF POLYCYTHEMIA VERA
PV therapy must address both short- and long-term objectives.
In the short term, therapeutic aims are to reduce the
risk of occurrence and recurrence of thrombosis, fırst via reduction
of the hematocrit—a simple parameter reflecting
blood viscosity. However, although very simple to use and
reliable, hematocrit is not the unique suspect, and many
other abnormalities play a role in the occurrence of thrombosis
in patients with PV. Quantitative but also qualitative
abnormalities (with features of aberrant activation) of leukocytes,
platelets, and even red cells have been reported to take
part in the prothrombotic state of patients with PV (and,
more generally, with MPN). 17,18 Finally, general cardiovascular
risk factors (e.g., smoking, hypertension, diabetes, dyslipidemia)
should not be neglected and require a particularly
careful evaluation in patients with PV, because thrombosis is
often multifactorial and caused by an accumulation of adverse
factors. A strict control of these standard risk factors,
therefore, is a major component of successful PV therapy.
Regardless of their risk category, treatment recommendations
1 for all patients with PV include antiplatelet therapy
with low-dose aspirin (100 mg/day) and phlebotomy to
maintain a hematocrit less than 45%. Patients who are age 60
or older and/or who have a history of thrombosis are highrisk
patients and should receive cytoreduction with HU or
recombinant IFN-alfa. HU is the preferred option for highrisk
patients in many countries where the off-label use of
IFN-alfa is not possible (Table 1).
First-Line Therapy
Phlebotomy can be an emergency therapy at diagnosis, in patients
who present with very high hematocrit and clinical
signs of hyperviscosity, as well as a long-term maintenance
therapy to control the hematocrit in low-risk patients. 19 The
optimal target of hematocrit levels was a matter of debate, but
a recent multicenter, randomized clinical trial (Cyto-PV)
showed that a hematocrit maintained strictly at less than 45%
during follow-up periods was signifıcantly associated with a
lower incidence of thrombosis (p 0.007). 19 Low-dose aspirin
is the second cornerstone of PV therapy, because it
has been shown in a large European, double-blind, placebocontrolled,
randomized trial (the ECLAP study) to signifıcantly
reduce a primary combined endpoint that included cardiovascular
death, nonfatal myocardial infarction, nonfatal stroke, and
major venous thromboembolism. 6
In addition to this strategy, a cytoreductive drug should be
prescribed in high-risk patients with PV (i.e., age older than
60 and/or with a history of a vascular event). The European
LeukemiaNet (ELN) recommendations for the management
of PV suggested that HU and IFN-alfa were the cytoreductive
treatments of choice as fırst-line therapy for high-risk patients
with PV. 1 HU is a well-known drug with good effıcacy
and tolerance in the majority of patients. This effıcacy is often
TABLE 1. Risk-Based Therapy of Polycythemia Vera
and Essential Thrombocythemia
Risk-Based Treatment Group PV ET
All Patients
Management of cardiovascular risk factors
Low-Risk Patients Aspirin Aspirin
Phlebotomy
High-Risk Patients
First line HU or IFN-alfa HU
Second line Switch IFN-alfa or HU Anagrelide
Ruxolitinib
Other Busulfan IFN-alfa
Abbreviations: PV, polycythemia vera; ET, essential thrombocythemia; HU, hydroxyurea; IFN,
interferon.
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