[Hydroxyurea--is it a harmless drug in Vaquez disease?]]

Area of Science:

• Hematology
• Oncology

Background:

• Polycythemia Vera (PV) is a myeloproliferative neoplasm.
• Long-term treatment for PV often involves cytoreductive agents like Hydroxy-urea.
• Concerns exist regarding the safety profile of Hydroxy-urea, particularly its long-term effects.

Purpose of the Study:

• To evaluate the safety and efficacy of Hydroxy-urea in Polycythemia Vera patients.
• To assess the incidence of side effects and the risk of secondary malignancies associated with Hydroxy-urea therapy.

Main Methods:

• Prospective trial of 150 PV patients treated with Hydroxy-urea alone (median follow-up: 9 years).
• Prospective trial of 181 elderly PV patients receiving Hydroxy-urea as maintenance therapy after 32P treatment (median follow-up: 9 years).
• Analysis of side effect incidence, treatment discontinuation rates, and actuarial risk of leukemia or myelodysplasia.

Main Results:

• Hydroxy-urea monotherapy caused side effects in 29% of patients, leading to treatment cessation in 50% of these cases.
• The incidence of leukemia or myelodysplasia was 6.7%, with an estimated 10% actuarial risk of leukemic transformation at 13 years.
• In the maintenance therapy arm, Hydroxy-urea use was associated with a two-fold increase in leukemic risk compared to controls (e.g., 35% vs. 16% at 15 years).
• Side effects were observed in 13% of patients receiving Hydroxy-urea as maintenance therapy.

Conclusions:

• Hydroxy-urea is associated with significant side effects and a notable risk of secondary leukemia and myelodysplasia in Polycythemia Vera patients.
• The leukemogenic potential of Hydroxy-urea, especially in maintenance therapy, warrants careful consideration and may necessitate alternative treatment strategies.
• Long-term Hydroxy-urea treatment for Polycythemia Vera is not without considerable risks, challenging its status as an 'innocent' drug.