Originally published as JCO Early Release 10.1200/JCO.2007.15.3569 on April 28 2008

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Leukocytosis and Risk Stratification Assessment in Essential Thrombocythemia

Alessandra Carobbio, Elisabetta Antonioli, Paola Guglielmelli, Alessandro M. Vannucchi, Federica Delaini, Vittoria Guerini, Guido Finazzi, Alessandro Rambaldi, Tiziano Barbui

From the Hematology Department, Ospedali Riuniti di Bergamo; Hematology Department, Università degli Studi di Firenze; Transfusion Medicine Department, Ospedali Riuniti di Bergamo, Italy

Corresponding author: Tiziano Barbui, MD, Divisione di Ematologia, Ospedali Riuniti Largo Barozzi 1, 24100 Bergamo, Italy; e-mail: tbarbui{at}ospedaliriuniti.bergamo.it

Purpose: Established risk factors for thrombosis in essential thrombocythemia (ET) include age and previous vascular events. We aimed to refine this risk stratification by adding baseline leukocytosis.

Patients and Methods: We enrolled 657 patients with ET followed for a median of 4.5 years who developed 72 major thrombosis. Cox proportional hazard model was performed to analyze the thrombotic risk and to discriminate ET patients with or without thrombosis, multivariable C statistic index was used. We searched for leukocytes cutoff with the best sensitivity and specificity by a receiver operating characteristic curve.

Results: Results confirmed that age and prior events are independent risk factors for thrombosis and showed a gradient between baseline leukocytosis and thrombosis. On the contrary, no significant association was found either for JAK2^V617F allele burden and for other laboratory parameters, including platelet number. In the model with conventional risk factors alone, C statistic ratio for total thrombosis was 0.63 and when leukocytosis was added, the change was small (C = 0.67). In contrast, in younger and asymptomatic patients (low-risk category), C statistic value indicated an high risk for thrombosis in patients with leukocytosis, similar to that calculated in conventionally defined high-risk group (C = 0.65). The best leukocyte cutoff values for predicting the events was found to be 9.4 (x 10⁹/L).

Conclusion: We suggest to include baseline leukocytosis in the risk stratification of ET patients enrolled in clinical trials.

published online ahead of print at www.jco.org on April 28, 2008.

Supported by the Associazione Italiana per la Ricerca sul Cancro (V.G.; Schenker-Erico Ghezzi fellowship); the Fondazione Italiana per la Ricerca sul Cancro (A.C.; fellowship), European LeukemiaNet Sixth Framework Programme LSH-2002-2.2.0-3; Ricerca finalizzata 2005 –IRCCS Policlinico "San Matteo", Clinical Trials Consortium; Myeloproliferative Disease Research Consortium, MIUR Cofin 2006067001_003 (A.M.V.); Associazione Paolo Belli; and by Associazione Italiana Lotta alla Leucemia AIL, sezione Paolo Belli.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.