Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera. (21st December 2015)

• Record Type: Journal Article
• Authors: Alvarez‐Larrán, Alberto; Kerguelen, Ana; Hernández‐Boluda, Juan C.; Pérez‐Encinas, Manuel; Ferrer‐Marín, Francisca; Bárez, Abelardo; Martínez‐López, Joaquín; Cuevas, Beatriz; Mata, M. Isabel; García‐Gutiérrez, Valentín; Aragües, Pilar; Montesdeoca, Sara; Burgaleta, Carmen; Caballero, Gonzalo; Hernández‐Rivas, J. Angel; Durán, M. Antonia; Gómez‐Casares, M. Teresa; Besses, Carles
• Is Part Of: British journal of haematology. Volume 172:Number 5(2016)
• Page Start: 786
• Page End: 793
• Publication Date: 2015-12-21
• Subjects: myeloproliferative neoplasms -- polycythaemia vera -- hydroxycarbamide -- resistance/intolerance -- response criteria; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13886
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: The clinical significance of resistance/intolerance to hydroxycarbamide (HC) was assessed in a series of 890 patients with polycythaemia vera (PV). Resistance/intolerance to HC was recorded in 137 patients (15·4%), consisting of: need for phlebotomies (3·3%), uncontrolled myeloproliferation (1·6%), failure to reduce massive splenomegaly (0·8%), development of cytopenia at the lowest dose of HC to achieve a response (1·7%) and extra‐haematological toxicity (9%). With a median follow‐up of 4·6 years, 99 patients died, resulting in a median survival of 19 years. Fulfilling any of the resistance/intolerance criteria had no impact on survival but when the different criteria were individually assessed, an increased risk of death was observed in patients developing cytopenia [Hazard ratio (HR): 3·5, 95% confidence interval (CI): 1·5–8·3, P = 0·003]. Resistance/intolerance had no impact in the rate of thrombosis or bleeding. Risk of myelofibrotic transformation was significantly higher in those patients developing cytopenia (HR: 5·1, 95% CI: 1·9–13·7, P = 0·001) and massive splenomegaly (HR: 9·1, 95% CI: 2·3–35·9, P = 0·002). Cytopenia at the lowest dose required to achieve a response was also an independent risk factor for transformation to acute leukaemia (HR: 20·3, 95% CI: 5·4–76·5, P < 0·001). In conclusion, the unified definition of resistance/intolerance to HC delineates a heterogeneous group of PV patients, with those developing cytopenia being associated with an adverse outcome.