p53 expression by immunohistochemistry is an important determinant of survival in patients with chronic lymphocytic leukemia receiving frontline chemo-immunotherapy.

Although chromosome 17p abnormalities and TP53 mutations have been reported as poor prognostic indicators in chronic lymphocytic leukemia (CLL), the impact of aberrant p53 expression as assessed by immunohistochemistry (p53-IHC) has not been defined in patients with CLL treated with chemoimmunotherapy, particularly in the context of other novel markers such as ZAP-70 expression and IgVH mutation status (IgVH MS). We assessed p53-IHC in 222 bone marrow (BM) specimens from patients with CLL enrolled in a phase II trial with fludarabine, cyclophosphamide, and rituximab (FCR). ZAP70 expression and IgVH MS were assessed in 208 and 108 patients, respectively. One hundred sixty-eight patients had concurrent classical cytogenetic analysis. p53-IHC correlated with abnormal karyotype (p = 0.002) and adversely affected overall survival independent of ZAP70 expression and IgVH MS (p < 0.001). Patients with p53-IHC(+) CLL were less likely to achieve complete remission, but patients who did achieve complete remission showed a durable response. In this patient cohort, p53-IHC is an important determinant of complete remission and overall survival, but not remission duration, in patients with CLL receiving FCR.