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

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Relative value Of ZAP-70, CD38, and immunoglobulin mutation status in predicting

aggressive disease in chronic lymphocytic leukemia.

Z Rassenti, Jain, J Keating, G Wierda, R

Grever, C Byrd, Neil E Kay, R Brown, G Gribben, Donna S

Neuberg, Feng He, W Greaves, Kanti R Rai, and J Kipps

Blood, June 24, 2008; .

Hematology/Oncology, s Cancer Ctr, University of California, San Diego, La

Jolla, CA, United States.

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 two groups of intermediate-risk or low-risk

disease based upon 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 one 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

intial therapy by standard criteria of approximately three years.

PMID: 18577710