Risk of thrombosis according to need of phlebotomies in patients with polycythemia vera treated with hydroxyurea.
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.
Hospital del Mar, IMIM, UAB, Barcelona, Spain 95967@parcdesalutmar.cat.
Alberto
A
Alvarez-Larrán
Hospital Clínico, Santiago de Compostela, Spain.
Manuel
M
Pérez-Encinas
Hospital Morales-Messeguer, IMIB, UCAM, Murcia, Spain.
Francisca
F
Ferrer-Marín
Hospital Clínico, Valencia, Spain.
Juan Carlos
JC
Hernández-Boluda
Hospital de Jerez, Jerez de la Frontera, Spain.
María José
MJ
Ramírez
Hospital 12 de Octubre, Madrid, Spain.
Joaquín
J
Martínez-López
Hospital Príncipe de Asturias, Alcalá de Henares, Spain.
Elena
E
Magro
Hospital del Mar, IMIM, UAB, Barcelona, Spain.
Yasmina
Y
Cruz
Hospital de la Costa del Sol, Marbella, Spain.
María Isabel
MI
Mata
Hospital de Cruces, Bilbao, Spain.
Pilar
P
Aragües
Hospital Vall d'Hebron, Barcelona, Spain.
María Laura
ML
Fox
Hospital de Burgos, Burgos, Spain.
Beatriz
B
Cuevas
Hospital del Mar, IMIM, UAB, Barcelona, Spain.
Sara
S
Montesdeoca
Hospital Infanta Leonor, Madrid, Spain.
José Angel
JA
Hernández-Rivas
Hospital Ramón y Cajal, Madrid, Spain.
Valentín
V
García-Gutiérrez
Hospital Dr Negrín, Las Palmas de Gran Canaria, Spain.
María Teresa
MT
Gómez-Casares
Hospital Universitario de la Princesa, Madrid, Spain.
Juan Luis
JL
Steegmann
Hospital Son Espases, Palma de Mallorca, Spain.
María Antonia
MA
Durán
Hospital Clínico, Valencia, Spain.
Montse
M
Gómez
Hospital La Paz, Madrid, Spain.
Ana
A
Kerguelen
Complejo assistencial de Avila, Avila, Spain.
Abelardo
A
Bárez
Hospital General de Alicante, Spain.
Mari Carmen
MC
García
Hospital Duran i Reinals, Institut Català d'Oncologia, Hospitalet de Llobregat, Spain.
Concepción
C
Boqué
Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
José María
JM
Raya
Hospital de Sant Pau, Barcelona, Spain.
Clara
C
Martínez
Complexo Hospitalario Universitario de Ourense, Spain.
Manuel
M
Albors
Hospital del Mar, IMIM, UAB, Barcelona, Spain.
Francesc
F
García
Hospital Príncipe de Asturias, Alcalá de Henares, Spain.
Carmen
C
Burgaleta
Hospital del Mar, IMIM, UAB, Barcelona, Spain.
Carlos
C
Besses
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001772:Blood Cell Count; D003131:Combined Modality Therapy; D004351:Drug Resistance; D005260:Female; D006400:Hematocrit; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D018962:Phlebotomy; D011087:Polycythemia Vera / Q000150:complications* / Q000175:diagnosis / Q000628:therapy*; D012042:Registries; D012306:Risk; D013030:Spain / Q000453:epidemiology; D013927:Thrombosis / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D006918:Hydroxyurea
Blood. 2002 Dec 15;100(13):4272-90
12393615
Blood. 2012 Feb 9;119(6):1363-9
22160617
J Clin Oncol. 2011 Feb 20;29(6):761-70
21205761
Blood. 2007 Aug 15;110(4):1092-7
17488875
Br J Haematol. 2010 Mar;148(6):961-3
19930182
N Engl J Med. 2013 Jan 3;368(1):22-33
23216616
Ann Intern Med. 1995 Nov 1;123(9):656-64
7574220
Br J Haematol. 2016 Mar;172(5):786-93
26898196
Br J Haematol. 2016 Feb;172(3):337-49
26492433
Nature. 2005 Apr 28;434(7037):1144-8
15793561
J Clin Oncol. 2005 Apr 1;23(10):2224-32
15710945
Haematologica. 2009 Nov;94(11):1484-8
19880775
Blood. 2007 Mar 15;109(6):2446-52
17105814
Lancet. 1978 Dec 9;2(8102):1219-22
82733