The third era begins with the emergence of the Rai staging system and we will end our discussion of it with Rai et al.'s 2000 comparison of chlorambucil with a new drug for CLL called fludarabine (47). In this modern era, two major areas for investigation became evident. First, because extremely wide range of survival time in this disease, clinicians were frustrated by the difficulty of making therapeutic decisions in patients newly diagnosed with CLL. Second, we needed a better understanding of the abnormalities of the leukemic cell in CLL and how it might predict prognosis; such an understanding would help us to understand normal B-cell differentiation.
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