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document
PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia . Addition of rituximab ( R ) to fludarabine and cyclophosphamide ( FC ) has significantly improved patient outcomes in chronic lymphocytic leukemia ( CLL ) . Whether baseline gene expression can identify patients who will benefit from immunochemotherapy over chemotherapy alone has not been determined . We assessed genome-wide expression of 300 pretreatment specimens from a subset of 552 patients in REACH , a study of FC or R-FC in relapsed CLL . An independent test set was derived from 282 pretreatment specimens from CLL8 , a study of FC or R-FC in treatment-naïve patients . Genes specific for benefit from R-FC were determined by assessing treatment-gene interactions in Cox proportional hazards models . REACH patients with higher pretreatment protein tyrosine kinase 2 ( PTK2 ) messenger RNA levels derived greater benefit from R-FC , with significant improvements in progression-free survival , independent of known prognostic factors in a multivariate model . Examination of PTK2 gene expression in CLL8 patients yielded similar results . Furthermore , PTK2 inhibition blunted R-dependent cell death in vitro . This retrospective analysis from 2 independent trials revealed that increased PTK2 expression is associated with improved outcomes for CLL patients treated with R-FC vs FC . PTK2 expression may be a useful biomarker for patient selection in future trials . These trials were registered at www.clinicaltrials.gov as # NCT00090051 ( REACH ) and # NCT00281918 ( CLL8 ) .
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Intervention_Pharmacological
rituximab ( R ) to fludarabine and cyclophosphamide
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Intervention_Pharmacological
FC
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Intervention_Pharmacological
R-FC
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Outcome_Physical
patient outcomes
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Outcome_Physical
genome-wide expression
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Outcome_Mortality
progression-free survival
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Outcome_Physical
R-dependent cell death
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Participant_Condition
chronic lymphocytic leukemia
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Participant_Condition
chronic lymphocytic leukemia
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Participant_Condition
CLL
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Participant_Sample-size
300
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Participant_Sample-size
552
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Participant_Condition
CLL