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Treatment of Chronic Lymphocytic Leukemia


Treatment recommendations

Chlorambucil (6–8 courses)

  • Continual: 0.08–0.12 mg/kg
  • Intermittently:  
    •  10 mg/m2 for 10 days, every 28 days
    •  30 mg/m2 in 4 doses, 1 day every 14 days  
    •  15 mg/m2 for 4 days, every 28 days
  • High continually: 10 mg/m2 until response or toxicity

Fludarabine (6–8 courses) 

  • 40 mg/m2 for 5 days, every 28 days

Fludarabine/ Cyclophosphamide (6–8 courses) 

  • 40 mg/m2 for 3 days, every 28 days
  • 250 mg/m2 for 3 days, every 28 days
  • Possible addition of rituximab recommended as 375 mg/m2 at first course and 500 mg/m2 for subsequent courses.

Treatment for recurrence

There are no clear recommendations regarding treatment for recurrence after first line treatment. If the need for further treatment appears after 2 years or more, there are good chances that first line treatment can achieve a new response. No response or early recurrence indicates that alternative treatment regimens should be tried. 

For chlorambucil resistance, the next obvious choice is a fludarabin treatment regimen. If fludarabin monotherapy was used as first line treatment, an alternative is combination treatment supplemented with monoclonal antibody (rituximab (anti-CD20 antibody) or alemtuzumab). Newer clinical studies indicate that fludarabin resistance is associated with very poor prognosis and experimental treatment including allogeneic stem cell transplantation should be considered for these patients. 

At present, an allogeneic stem cell transplantation should only take place within evaluable clinical studies.


Certain patients have significant splenomegaly and lymphocyte infiltration in the bone marrow with relatively moderate lymphocytosis in the blood. In these patients, the spleen can cause troublesome local symptoms or cause anemia and thrombocytopenia due to hypersplenism. In these situations, a splenectomy is a good treatment alternative. A splenectomy may also be worth trying with immune hemolysis or thrombocytopenia which responds poorly to adequate steroid doses.


Patients with chronic lymphocytic leukemia often have an increased tendency for infections which may be due to granulocytopenia or, more frequently, hypogammaglobulinemia. In these patients with serious infection complications, which are reasonable to believe are secondary to gammaglobulinemia (infections with capsule-covered bacteria), there is a documented effect from prophylaxis substitution treatment with gammaglobulin. It is important to be aware that many patients have significant hypogammaglobulinemia without infection tendencies. In these patients, there is no indication for substitution treatment.

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