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

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.

journal_name

Blood

journal_title

Blood

authors

Rassenti LZ,Jain S,Keating MJ,Wierda WG,Grever MR,Byrd JC,Kay NE,Brown JR,Gribben JG,Neuberg DS,He F,Greaves AW,Rai KR,Kipps TJ

doi

10.1182/blood-2007-05-092882

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

1923-30

issue

5

eissn

0006-4971

issn

1528-0020

pii

blood-2007-05-092882

journal_volume

112

pub_type

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