Valerio De Stefano,1* Tommaso Za,1 Elena Rossi,1 Alessandro M. Vannucchi,2 Marco Ruggeri,3 ` Elena Elli,4 Caterina Mico,5 Alessia Tieghi,6 Rossella R. Cacciola,7 Cristina Santoro,8 Giancarla Gerli,9 Paola Guglielmelli,2 Lisa Pieri,2 FrancescaScognamiglio,3 Francesco Rodeghiero,3 Enrico M. Pogliani,4 Guido Finazzi,5 Luigi Gugliotta,6 Giuseppe Leone,1 Tiziano Barbui,5 For the GIMEMA Chronic Myeloproliferative Neoplasms Working Party
There is evidence that leukocytosis is associated with an increased risk of ﬁrst thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Whether it is a risk factor for recurrentthrombosis too is currently unknown. In the frame of a multicenter retrospective cohort study, we recruited 253 patients with PV (n 5 133) or ET (n 5 120), who were selected on the basis of a ﬁrst arterial (70%) or venous major thrombosis (27.6%) or both (2.4%), and who were not receiving cytoreduction at the time of thrombosis. The probability of recurrent thrombosis associated with theleukocyte count recorded at the time of the ﬁrst thrombosis was estimated by a receiver operating characteristic analysis and a multivariable Cox proportional hazards regression model. Thrombosis recurred in 78 patients (30.7%); multivariable analysis showed an independent risk of arterial recurrence (hazard ratio [HR] 2.16, 95% CI 1.12–4.18) in patients with a leukocyte count that was >12.4 3 109/L atthe time of the ﬁrst thrombotic episode. The prognostic role for leukocytosis was age-related, as it was only signiﬁcant in patients that were aged 60 years is also an independent risk factor for recurrences, and cytoreduction signiﬁcantly protects against novel events . In this study, we investigated the prognostic role of leukocytosis that was registered at the time of the ﬁrst event topredict future recurrent thrombotic events. Patients and Methods
Study patients. A retrospective study was conducted using the medical records of 494 patients with PV and ET who were diagnosed at one of the hematological centers of GIMEMA (Gruppo Italiano Malattie Ematologiche dell’Adulto) from January 1985 to December 2005. The main criterion for inclusion in the study was that all 494 individuals hadsuffered at least one major thrombotic event related to their haematological disease. Details of the procedure used to recruit the cohort have been reported elsewhere . In this analysis, we only investigated the patients who were not receiving any cytoreductive treatment and had a recorded white blood cell (WBC) count at the time of the initial thrombosis. Deﬁnition of the events and of therisk factors. A thrombotic event related to the patient’s hematologic disease was deﬁned as an event that occurred following diagnosis and referral to the specialized hematological center, or an event that occurred no earlier than 2 years preceding the diagnosis. Thrombotic events that occurred more than 2 years before the hematologic disease diagnosis were considered to be remote thromboses. Themajor thrombotic events of interest were ischemic stroke, transient ischemic attack (TIA), acute myocardial infarction, unstable angina pectoris, peripheral arterial thrombosis, retinal artery or vein
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1 The Institute of Hematology, Catholic University, Rome, Italy; 2Department of Hematology, University of Florence, Florence, Italy; 3Department of Hematology andHemophilia and Thrombosis Center, San Bortolo Hospital, Vicenza, Italy; 4Hematology Division and Bone Marrow Transplantation Unit, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy; 5Department of Hematology-Oncology, Ospedali Riuniti, Bergamo, Italy; 6Hematology Unit, Santa Maria Nuova Hospital, Reggio Emilia, Italy; 7Department of Biomedical Sciences, Section of Hematology, University of...