Most patients with CLL demonstrate a stable histology throughout their clinical course; however, a minority may show evolution to more aggressive disease forms, including Richter's syndrome, prolymphocytoid transformation, and rarely, acute leukemia.165

Richter's transformation occurs in 5 to 10 percent of CLL cases and represents a change to a large-cell lymphoma (LCL) histology.166 Robertson et al.167 described 39 CLL patients in whom LCL developed. This represented 3 percent of patients enrolled in a computer-based registry at MDACC between 1972 and 1992.167 Patients in whom LCL was noted included patients in all Rai stages and in 10 patients in remission after fludarabine therapy. The incidence of transformation after fludarabine or 2-CdA therapy was not significantly increased over that in patients treated with alkylating agents. Systemic symptoms and progressive lymphadenopathy were seen in most patients. Extranodal involvement and paraproteinemia were seen in 41

percent and 44 percent, respectively. The most frequent laboratory abnormality was elevation of lactate dehydrogenase (LDH); 82 percent of patients had a value more than twice normal. Only 8 percent of patients with CLL seen at MDACC had this level of LDH elevation. As seen in other studies, median survival was short (5 months), although patients responding to chemotherapy lived longer.168-171

The development of acute leukemia or multiple myeloma in patients with CLL is a rare phenomenon, occurring in less than 1 percent of cases and has not been well characterized.165,172 Isolated cases of CLL transformation into small noncleaved cell lymphoma,173 lymphoblastic lymphoma,174 hairy cell leukemia,175 and Hodgkin's disease176 have been reported.

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