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Blood, 1 August 2006, Vol. 108, No. 3, pp. 1001-1006.
Prepublished online as a Blood First Edition Paper on March 21, 2006; DOI 10.1182/blood-2005-05-2110.
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NEOPLASIA
Plasma thrombopoietin compared with immunoglobulin heavy-chain mutation status as a predictor of survival in chronic lymphocytic leukemia
Charles Koller,
B. Nebiyou Bekele,
Xian Zhou,
Charles Park,
Zeev Estrov,
Susan O'Brien,
Michael Keating,
Iman Jilani,
Francis J. Giles,
Hagop M. Kantarjian, and
Maher Albitar
From the Departments of Leukemia and Biostatistics and Applied Mathematics, University of Texas, M. D. Anderson Cancer Center, Houston, TX; and the Department of Hematopathology, Nichols Institute, Quest Diagnostics, San Juan Capistrano, CA.
We investigated the association of plasma thrombopoietin (TPO) and overall survival in 127 patients with previously treated and previously untreated chronic lymphocytic leukemia (CLL). Higher levels of TPO were associated with advanced Rai stage (P < .001), higher levels of  2-microglobulin (2-M) (P < .001), and the absence of mutation in the immunoglobulin heavy chain variable region (IgVH) (P < .001), and were inversely correlated with platelet count (P = .002). We found that TPO correlated strongly in a continuous manner with overall survival in both previously treated and untreated patients. The univariate Cox proportional hazard model demonstrated that high TPO levels were associated with shorter survival (P < .001), and multiple variable Cox proportional hazards regression analysis demonstrated that this was independent of the IgVH mutation status, 2-M, and Rai stage. Recursive partitioning showed that a cutoff point of 639 pg/mL separated the CLL patients into 2 major survival groups (P < .001). The effects of 2-M were masked by the effects of TPO in the patients with TPO levels higher than 639 pg/mL, but in the remainder, patients with 2-M level higher than 4.95 mg/L had significantly shorter survival than those with lower values. Plasma TPO and 2-M may be useful for the prediction of clinical behavior in CLL and may replace the need for the determination of IgVH mutation status.
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