Plasma Thrombopoietin May be Useful Prognostic Indicator in CLL

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Blood First Edition Paper, prepublished online March 21, 2006

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

Koller, B N Bekele, Xian Zhou, Park, Zeev Estrov,

O'Brien, Keating, Iman Jilani, Francis J Giles, Hagop M

Kantarjian, and Maher Albitar*

Department of Leukemia, University of Texas M.D. Cancer

Center, Houston, TX, USA

Departments of Biostatistics and Applied Mathmatics, University of

Texas M.D. Cancer Center, Houston, TX, USA

Department of Hematopathology, Quest Diagnostics Nichols Institute,

San Capistrano, CA, USA

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 beta-2-microglublin (B-

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 proportional hazard model demonstrated that high

TPO levels were associated with shorter survival (P<0.0001) and

multiple variable proportional hazards regression analysis

demonstrated that this was independent of the IgVH mutation status, B-

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 B-2M were masked by the effects of TPO in the patients

with TPO >639.4 pg/ml, but in the remainder, patients with B-2M >4.95

had significantly shorter survival than those with lower values.

Plasma TPO and B-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.