Management of symptomatic, untreated chronic lymphocytic leukemia

Fludarabine-based regimens have become an increasingly popular first-line approach for symptomatic patients with chronic lymphocytic leukemia. Compared with chlorambucil, fludarabine alone or in combination with cyclophosphamide or rituximab yields higher response rates, higher complete remission rates, and more durable progression-free survival. Immunotherapy and chemoimmunotherapy also have the potential to increase the depth of remission as assessed by flow cytometry or molecular techniques. An overall survival advantage with any one particular regimen has not yet been demonstrated. Progress with fludarabine-based regimens, monoclonal antibodies, chemoimmunotherapy, and high-dose therapy for previously untreated patients is reviewed. Fluorescent in situ hybridization and immunoglobulin variable heavy-chain sequencing now permit more individualized risk assessment. Examples of possible treatment algorithms based on risk category are explored. How to tailor treatment based on these newer prognostic factors remains a central, as yet unanswered management question.