The current recommendation for patients with early-stage CLL is that treatment should not be initiated without specific indications (i.e., symptomatic progression or a rapid lymphocyte doubling time). This recommendation is based on data demonstrating that currently available therapies do not cure patients with CLL, yet may be associated with significant toxicities (22).

For patients with advanced disease, the most active classes of chemotherapy drugs are alkylating agents (chlorambucil and cyclophosphamide), nucleoside analogs (flu-darabine, cladribine, and pentostatin), and monoclonal antibodies (MAbs; alem-tuzamab). Myelosuppression is a frequent and often dose-limiting consequence of therapy with these agents.

1.5.1. First-Line Therapy

Fludarabine is the preferred initial treatment for most patients with CLL (23-25). Because of toxicities associated with fludarabine, chlorambucil-based regimens are a first-line treatment option for frail elderly patients, patients with reduced performance status, or those with active infections.

1.5.2. Second-Line Therapies

Fludarabine is the standard agent for second-line therapy of patients who received front-line alkylators. Alemtuzumab has clinical activity in patients refractory to fludarabine and/or alkylating agents (26).

1.5.3. Stem Cell Transplantation

Autologous stem cell transplants are under investigation in CLL. Such transplants usually involve positive and/or negative purging procedures to address the significant amount of leukemic cell contamination in the stem cell source. Data about allogeneic marrow or stem cell transplant are limited in CLL. Given the advanced age at diagnosis (>60 yr) and the fact that currently available therapies rarely eradicate detectable disease, patients with CLL are a high risk for transplantation. Both traditional and sub-myeloablative allogenic transplants are investigational at this time.

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