The Use of Fludarabine in Chronic Lymphocytic Leukemia and Malignant Lymphomas
Fludarabine is a new purine analogue which has demonstrated activity in low grade lymphoproliferative disorders. Initially, fludarabine was noted to have activity against lymphoma in phase I studies. Subsequently, major activity was demonstrated in the treatment of patients with previously treated and refractory chronic lymphocytic leukemia (CLL). The use of fludarabine (Fludara) in previously treated CLL is associated with a response rate of more than 50% with approximately one-third of patients obtaining a complete remission (CR) using NCI Working Group criteria. When Fludara is used in previously untreated patients with CLL, the response rate is 75–80% with the majority of responses being complete remissions. The median time-to-progression of CLL in responders is 18–27 months in previously treated patients and 42 months in previously untreated patients. The impact of Fludara on survival in these patient populations, so far, has not demonstrated in comparative trials. Fludara was noted to have activity against Waldenstrom’s macroglobulinemia in previously treated patient populations. More than half of these patients will respond, particularly those with primary refractory disease or disease relapsing off treatment. Refractory relapsed patients who have had multiple attempts at therapy have a lower response rate. The phase I activity of Fludara against malignant lymphoma has been confirmed in subsequent studies with the activity being noted predominantly in low grade lymphomas. Activity is minimal in intermediate and high grade lymphoma. Overall approximately 60% of patients with previously treated low grade lymphoma will respond to Fludara with 20% CRs. More recently Fludara has been combined with mitoxantrone and dexamethasone and is associated with a high CR+PR rate in low grade lymphomas. Fludara has an expanding role in the management of CLL and low grade lymphoma.
KeywordsComplete Remission Chronic Lymphocytic Leukemia Herpes Zoster Cytic Leukemia Refractory Chronic Lymphocytic Leukemia
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