Table 2

Comparison of the prognostic significance of ZAP-70, CD38, and IGHV mutation status on the time to initial treatment in the validation cohort by Cox proportional hazards univariate and multivariable regression analyses

CharacteristicValidation cohort, N = 705
Pretreatment samples, N = 521
All, N = 705Rai 0, n = 155Rai I/II, n = 330Rai III/IV, n = 220Older than 65 y, n = 152All, N = 521Rai 0, n = 134Rai I/II, n = 262Rai III/IV, n = 125Rai 0-II, n = 199§
ZAP-70 4.08* 4.45* 2.67* 2.51* 2.79* 5.36* 5.22† 2.36* 5.34* 4.85* 
    ZAP-70 /IGHV 3.09* 3.92* 1.90* 2.54* 2.41† 3.85* 4.47† 1.71 6.76* 4.34* 
    ZAP-70/CD38 3.96* 4.46* 2.63* 2.24* 2.84* 5.25* 5.21† 2.41* 4.61* 4.82* 
    ZAP-70/IGHV/CD38 3.01* 3.97* 1.88† 2.27* 2.47† 3.75* 4.63† 1.74 5.81* 4.31* 
IGHV 3.14* 2.22† 3.00* 1.28 2.14† 3.76* 2.53 2.61* 1.40 2.26† 
    IGHV/ZAP-70 1.87* 1.42 2.31* 0.97 1.43 1.98* 1.86 2.07† 0.59 1.46 
    IGHV/CD38 3.05* 2.14† 2.93* 1.19 2.15* 3.77* 2.44 2.61* 1.30 2.26† 
    IGHV/ZAP-70/CD38 1.86* 1.40 2.30* 0.94 1.42 1.99* 1.98 2.06† 0.61 1.45 
CD38 1.53* 0.57 1.35 1.73* 1.08 1.51† 0.50 1.06 2.24* 1.26 
    CD38/ZAP-70 1.14 0.56 1.06 1.45† 0.89 1.13 0.51 0.90 1.61† 1.08 
    CD38/IGHV 1.39† 0.60 1.19 1.71* 1.11 1.47† 0.52 1.03 2.21* 1.26 
    CD38/ZAP-70/IGHV 1.11 0.56 1.03 1.46† 0.91 1.13 0.47 .092 1.59† 1.06 
CharacteristicValidation cohort, N = 705
Pretreatment samples, N = 521
All, N = 705Rai 0, n = 155Rai I/II, n = 330Rai III/IV, n = 220Older than 65 y, n = 152All, N = 521Rai 0, n = 134Rai I/II, n = 262Rai III/IV, n = 125Rai 0-II, n = 199§
ZAP-70 4.08* 4.45* 2.67* 2.51* 2.79* 5.36* 5.22† 2.36* 5.34* 4.85* 
    ZAP-70 /IGHV 3.09* 3.92* 1.90* 2.54* 2.41† 3.85* 4.47† 1.71 6.76* 4.34* 
    ZAP-70/CD38 3.96* 4.46* 2.63* 2.24* 2.84* 5.25* 5.21† 2.41* 4.61* 4.82* 
    ZAP-70/IGHV/CD38 3.01* 3.97* 1.88† 2.27* 2.47† 3.75* 4.63† 1.74 5.81* 4.31* 
IGHV 3.14* 2.22† 3.00* 1.28 2.14† 3.76* 2.53 2.61* 1.40 2.26† 
    IGHV/ZAP-70 1.87* 1.42 2.31* 0.97 1.43 1.98* 1.86 2.07† 0.59 1.46 
    IGHV/CD38 3.05* 2.14† 2.93* 1.19 2.15* 3.77* 2.44 2.61* 1.30 2.26† 
    IGHV/ZAP-70/CD38 1.86* 1.40 2.30* 0.94 1.42 1.99* 1.98 2.06† 0.61 1.45 
CD38 1.53* 0.57 1.35 1.73* 1.08 1.51† 0.50 1.06 2.24* 1.26 
    CD38/ZAP-70 1.14 0.56 1.06 1.45† 0.89 1.13 0.51 0.90 1.61† 1.08 
    CD38/IGHV 1.39† 0.60 1.19 1.71* 1.11 1.47† 0.52 1.03 2.21* 1.26 
    CD38/ZAP-70/IGHV 1.11 0.56 1.03 1.46† 0.91 1.13 0.47 .092 1.59† 1.06 

This table lists the HRs for cases with CLL cells that were ZAP-70 positive, expressed U-IGHV, or were positive for CD38 in a univariate analysis. This table also lists the HRs when these prognostic markers were combined in a multivariable analysis when one or both of the other prognostic markers were added to the model (ie, ZAP-70 plus IGHV). The validation cohort is segregated into subgroups by Rai stage, by age at the time of sample collection, by the patients who were or were not treated for CLL at the time of sample collection, or by patients with Rai stages 0 to 2 who had samples collected within 1 year of diagnosis (median, 0.24 years after diagnosis). The univariate and multivariable analyses were analyzed via the Cox proportional hazards regression model. Hazard ratio (HR) is the ratio of the hazard functions between 2 groups. Here, the reference group in the HR is the set of patients having the adverse marker and an increase risk for early treatment. An asterisk (*) is used to denote HRs that have a P value of less than .001; a (†) is used to denote a HR that has a P value of less than .05. The symbol (§) is used to denote the subgroup of patients with Rai stage 0 to 2 stage disease who had blood samples collected for these analyses within 1 year of diagnosis (median = 0.24) prior to receiving treatment.

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