The strengths of our study include its unique population-based, prospective design, the availability of prediagnostic blood samples, and the application of high-quality assays for the determination of the presence of prediagnostic B-cell clones. The study also had some limitations. Because of the design of the PLCO Cancer Screening Trial, blood samples at the time of CLL diagnosis were not available. To partially address this issue, we used existing clinical data regarding light-chain restriction in CLL diagnostic clones. When we compared the CLL clone with the prediagnostic clone of the same patient, we did not find any cases in which either kappa or lambda expression was discordant. These findings are consistent with the contention that the prediagnostic clone subsequently evolved into clinically detectable CLL. It may also be questioned whether the high frequency of MBL before CLL diagnosis represents, in part, a manifestation of undetected leukemia present months to years before the manifestations of CLL. However, for the majority of patients in our study, we believe this hypothesis is unlikely. The PLCO population is relatively health-conscious and has volunteered for and
