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. 2017 Jan;102(1):103-109.
doi: 10.3324/haematol.2016.152769. Epub 2016 Sep 29.

Risk of thrombosis according to need of phlebotomies in patients with polycythemia vera treated with hydroxyurea

Alberto Alvarez-Larrán  1 , Manuel Pérez-Encinas  2 , Francisca Ferrer-Marín  3 , Juan Carlos Hernández-Boluda  4 , María José Ramírez  5 , Joaquín Martínez-López  6 , Elena Magro  7 , Yasmina Cruz  8 , María Isabel Mata  9 , Pilar Aragües  10 , María Laura Fox  11 , Beatriz Cuevas  12 , Sara Montesdeoca  8 , José Angel Hernández-Rivas  13 , Valentín García-Gutiérrez  14 , María Teresa Gómez-Casares  15 , Juan Luis Steegmann  16 , María Antonia Durán  17 , Montse Gómez  4 , Ana Kerguelen  18 , Abelardo Bárez  19 , Mari Carmen García  20 , Concepción Boqué  21 , José María Raya  22 , Clara Martínez  23 , Manuel Albors  24 , Francesc García  8 , Carmen Burgaleta  7 , Carlos Besses  8 ; Grupo Español de Neoplasias Mieloproliferativas Filadelfia Negativas
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Risk of thrombosis according to need of phlebotomies in patients with polycythemia vera treated with hydroxyurea

Alberto Alvarez-Larrán et al. Haematologica. 2017 Jan.

Abstract

Hematocrit control below 45% is associated with a lower rate of thrombosis in polycythemia vera. In patients receiving hydroxyurea, this target can be achieved with hydroxyurea alone or with the combination of hydroxyurea plus phlebotomies. However, the clinical implications of phlebotomy requirement under hydroxyurea therapy are unknown. The aim of this study was to evaluate the need for additional phlebotomies during the first five years of hydroxyurea therapy in 533 patients with polycythemia vera. Patients requiring 3 or more phlebotomies per year (n=85, 16%) showed a worse hematocrit control than those requiring 2 or less phlebotomies per year (n=448, 84%). There were no significant differences between the two study groups regarding leukocyte and platelet counts. Patients requiring 3 or more phlebotomies per year received significantly higher doses of hydroxyurea than the remaining patients. A significant higher rate of thrombosis was found in patients treated with hydroxyurea plus 3 or more phlebotomies per year compared to hydroxyurea with 0-2 phlebotomies per year (20.5% vs. 5.3% at 3 years; P<0.0001). In multivariate analysis, independent risk factors for thrombosis were phlebotomy dependency (HR: 3.3, 95%CI: 1.5-6.9; P=0.002) and thrombosis at diagnosis (HR: 4.7, 95%CI: 2.3-9.8; P<0.0001). The proportion of patients fulfilling the European LeukemiaNet criteria of resistance/intolerance to hydroxyurea was significantly higher in the group requiring 3 or more phlebotomies per year (18.7% vs. 7.1%; P=0.001) mainly due to extrahematologic toxicity. In conclusion, phlebotomy requirement under hydroxyurea therapy identifies a subset of patients with increased proliferation of polycythemia vera and higher risk of thrombosis.

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Figures

Figure 1.
Figure 1.
Hematocrit, leukocyte and platelet counts under hydroxyurea (HU) therapy. (A) Hematocrit in the whole cohort of patients. (B) Hematocrit in the two study groups (month 6, P<0.001; month 12, P=0.003; month 18, P=0.03; month 24, P=0.007; month 36, P=0.007; month 48, P<0.0001; month 60, P=0.1). (C) Leukocyte count in the two study groups (P=not significant). (D) Platelet count in the two study groups (P=not significant). 25th, 50th (median) and 75th percentiles are shown. HU: hydroxyurea; PHL: phlebotomies.
Figure 2.
Figure 2.
Time to resistance/intolerance to hydroxyurea according to European LeukemiaNet (ELN) criteria in patients with polycythemia vera treated with hydroxyurea (HU) and 3 or more phlebotomies per year (solid line) or with HU and 0–2 phlebotomies per year (dotted line). P=0.0001.
Figure 3.
Figure 3.
Time to thrombosis in patients with polycythemia vera treated with hydroxyurea (HU) and 3 or more phlebotomies per year (solid line) or with HU and 0–2 phlebotomies per year (dotted line). P<0.0001.
Figure 4.
Figure 4.
Time to bleeding (major or minor) in patients with polycythemia vera treated with hydroxyurea (HU) and 3 or more phlebotomies per year (solid line) or with HU and 0–2 phlebotomies per year (dotted line) (P=0.4).
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