Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia

LZ Rassenti, S Jain, MJ Keating… - Blood, The Journal …, 2008 - ashpublications.org
LZ Rassenti, S Jain, MJ Keating, WG Wierda, MR Grever, JC Byrd, NE Kay, JR Brown
Blood, The Journal of the American Society of Hematology, 2008ashpublications.org
Leukemia-cell expression of ZAP-70, CD38, or unmutated immunoglobulin heavy chain
variable region genes (U-IGHV) each is associated with aggressive disease in patients with
chronic lymphocytic leukemia (CLL). To assess the relative strength of each marker, we
defined thresholds for designating a case as positive for CD38 or ZAP-70 in a test cohort of
307 patients and used these data-defined criteria to stratify patients in an independent
cohort of 705 patients. Multivariable analysis revealed that ZAP-70 was the strongest risk …
Abstract
Leukemia-cell expression of ZAP-70, CD38, or unmutated immunoglobulin heavy chain variable region genes (U-IGHV) each is associated with aggressive disease in patients with chronic lymphocytic leukemia (CLL). To assess the relative strength of each marker, we defined thresholds for designating a case as positive for CD38 or ZAP-70 in a test cohort of 307 patients and used these data-defined criteria to stratify patients in an independent cohort of 705 patients. Multivariable analysis revealed that ZAP-70 was the strongest risk factor. Knowledge of the IGHV mutation status or CD38 did not improve our ability to predict the time to first treatment except for ZAP-70–negative cases, which could be segregated into 2 groups of intermediate-risk or low-risk disease based on whether they expressed unmutated or mutated IGHV. ZAP-70 maintained its high relative prognostic value for the subset of patients with early-stage, asymptomatic disease, including patients evaluated within 1 year of diagnosis. Although it is premature to recommend therapy based on these risk factors, patients with ZAP-70–positive CLL cells should be monitored closely for disease progression as they have a median time from diagnosis to requiring initial therapy by standard criteria of approximately 3 years.
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