Submitted May 26, 2005
Accepted February 27, 2006
Plasma thrombopoietin compared to immunoglobulin heavy-chain mutation status as a predictor of survival in chronic lymphocytic leukemia
Charles Koller, B N Bekele, Xian Zhou, Charles Park, Zeev Estrov, Susan O'Brien, Michael Keating, Iman Jilani, Francis J Giles, Hagop M Kantarjian, and Maher Albitar*
Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Departments of Biostatistics and Applied Mathmatics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Department of Hematopathology, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA
* Corresponding author; email: maher.x.albitar{at}questdiagnostics.com.
We investigated the association of plasma thrombopoietin (TPO) and overall survival in 127 patients with previously treated and previously untreated CLL. Higher levels of TPO were associated with advanced Rai stage (P<0.0001), higher levels
-2-microglublin (
-2M) (P<0.001), the absence of mutation in the immunoglobulin heavy chain variable region (IgVH ) (P<0.001), and were inversely correlated with platelet count (P=0.002). 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<0.0001) and multiple variableCox proportional hazards regression analysis demonstrated that this was independent of the IgVH mutation status,
-2M, and Rai stage. Recursive partitioning showed that a cut-off point of 639.4 pg/ml separated the CLL patients into two major survival groups (P<0.0001). The effects of
-2M were masked by the effects of TPO in the patients with TPO >639.4 pg/ml, but in the remainder, patients with
-2M >4.95 had significantly shorter survival than those with lower values.
Plasma TPO and
-2M may be useful for the prediction of clinical behavior in CLL and may be replace the need for the determination of IgVH mutation status.