Chronic lymphocytic leukemia in 2007: Prognostic factors and therapeutic approaches

Major prognostic factors in chronic lymphocytic leukemia (CLL) include chromosomal abnormalities that can be identified by conventional cytogenetic analysis or fluorescence in situ hybridization; 17p- and 11q- are associated with a poor prognosis; 6q- and 12q trisomy are associated with an intermediate prognosis; and 13q- (the most frequent cytogenetic abnormality in CLL) is a favorable marker. Other prognostic markers include presence (favorable) or absence of IgV_H somatic mutations, detected by polymerase chain reaction, and high levels of expression of CD38 and ZAP70 (both unfavorable) measured by flow cytometry. A recent study showed that median treatment-free survival was not reached in ZAP70-negative/CD38-negative patients (51% of study population), compared with 12 months in patients positive for both (17%) and 42 months in those positive for one (31%). However, the therapeutic utilization of these prognostic factors, over and above that dictated by clinical staging systems, remains to be determined. Regardless, it is currently reasonable to use cytogenetic information as well as ZAP70 and CD38 expression status to complement prognostication by clinical staging and to determine frequency of monitoring. When treatment is required, first-line treatment presently consists of FCR (fludarabine, cyclophosphamide, rituximab), which is associated with a 95% overall response rate and an unprecedented 70% complete remission rate. However, such therapy has not been shown to improve overall survival, and it is reasonable to continue considering first-line treatment with chlorambucil/prednisone instead for older patients. In general, patients with poor prognostic factors experience shorter progression-free survival after treatment, which is particularly true for patients with 17p-, who also respond poorly to standard therapy. A number of novel agents are in development for treatment of relapse. Allogeneic transplantation should not be omitted from consideration in relapse, because it offers a chance for cure.