Which study reported resistance or intolerance to hydroxyurea in 137 of 890 (15.4%) patients with polycythemia vera (PV)?

Updated: Sep 20, 2021
  • Author: Srikanth Nagalla, MD, MS, FACP; Chief Editor: Sara J Grethlein, MD, FACP  more...
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Alvarez-Larran et al reported resistance or intolerance to hydroxyurea in 137 of 890 (15.4%) patients with polycythemia vera. With a median survival of 19 years, resistance or intolerance had no impact on survival, but patients who developed cytopenia had increased risk of death (hazard ratio [HR] 3.5, P = 0.003) and of myelofibrotic transformation  (HR 5.1, P = 0·001). Cytopenia at the lowest dose required to achieve a response was also an independent risk factor for transformation to acute leukemia (HR 20.3,  P < 0.·001). [23]

Leukocytosis may be a risk factor for thrombosis. In a subanalysis of the Cytoreductive Therapy in Polycythemia Vera (CYTO-PV) trial, risk of thrombosis was increased in patients whose WBC exceeded 7000/µL, and reached statistical significance at levels of 11,000/µL and above (HR 3.90, P = 0.02). An association between elevated WBC counts and thrombosis has also been found in studies of patients with essential thrombocythemia. These authors recommend including the WBC count when evaluating response to cytoreductive therapy. [24]

Initial research has suggested a role for interferon alpha as a first-line treatment, athough toxicity can be problematic. Interferon alpha is not yet approved for use in PV, but phase III studies are ongoing. [11]

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