Treatment Options for Chronic Lymphocytic Leukemia (CLL)

Although no cure has been found yet for CLL, it is possible to feel well and live for years in good health. Treatment options are based on many factors including staging, the presence of symptoms such as fever or weight loss, or how a patient responds to treatment. Patients may be observed for many years without requirement for treatment but those who develop symptoms of advancing disease receive therapy in almost all cases.

The treatment of CLL primarily aims to:

  • Slow down the accumulation of CLL cells
  • Keep patients feeling well enough to carry on their day-to-day activities
  • Maintain a patient’s quality of life
  • Improve the number of normal blood cells (normal white cells, red cells and platelets).

 Standard treatment options for CLL include:

  • Watchful waiting
  • Drug therapy
    • Chemotherapy
    • Biologic therapy
  • Stem-cell transplantation
  • Radiation therapy
  • Splenectomy.

Some Factors That Influence the Decision to Treat Patients with CLL*

  • Relatively rapid increase of blood lymphocyte counts
  • Enlarging lymph nodes
  • Enlarging spleen
  • Worsening anemia
  • Falling platelet count.

*Several of these factors are often present at the same time.

Watchful Waiting (also called Watch and Wait)

Watchful waiting is a strategy where healthcare professionals monitor a patient’s condition closely, but withhold treatment until symptoms appear or change. This period is also called watch and wait or observation.

During the watch-and-wait period, you will need to meet with your cancer specialist for follow-up visits to see if there are any changes with your health.

The reason watchful waiting is used as an approach is because studies have not shown that immediate treatment prolongs survival. And since treatment affects healthy cells as well as the cancer cells, for now experts believe that treatment should be delayed until necessary. Some people may never require therapy.

Drug Therapy

Patients requiring treatment are often treated with drug therapy: chemotherapy and/or monoclonal antibody therapy. The choice of recommended treatment generally depends on the patient’s overall health status and the stage of his or her disease. Age may be a factor for certain types of therapy.


Fludarabine (Fludara®) is considered to be one of the most effective types of chemotherapy for CLL. Drug combinations, including fludarabine and cyclophosphamide (Cytoxan®)—FC; fludarabine and rituximab (Rituxan®)—FR; and fludarabine, cyclophosphamide and rituximab—FCR—are often used to treat patients with intermediate- and high-risk CLL. Studies comparing treatment with fludarabine alone to treatment with FC, or to treatment with various FCR regimens, have shown that combination treatments significantly improve the frequency of complete response in previously untreated people with CLL. Additional studies in clinical trials are needed to determine which patients will benefit from FCR versus other CLL treatments. In addition, treatments combining fludarabine with other drugs are currently being studied in clinical trials.

Bendamustine (Treanda®) is another type of chemotherapy that is approved for the treatment of CLL in some provinces. Combinations of bendamustine and other drugs, including rituximab and lenalidomide (Revlimid®), are currently being studied in clinical trials for the treatment of people with CLL.

Patients with CLL may receive chemotherapy as a single drug. Examples include:

  • Chlorambucil may be administered orally with few immediate side effects
  • Fludarabine is administered orally or intravenously and can be associated with some side effects.

Many patients with CLL will receive a combination chemotherapy regimen such as:

  • FC chemotherapy (fludarabine and cyclophosphamide)
  • CVP chemotherapy (cyclophosphamide, vincristine and prednisone)
  • CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone).

Patients should be aware of all of their treatment options and speak to their doctors about selecting the best treatment for them.

Biologic Therapy

Biologic therapy is a treatment that stimulates or restores the ability of your immune system to fight disease or infections.

Monoclonal antibodies are proteins that are bioengineered in the laboratory. Each monoclonal antibody therapy is designed to recognize a specific molecule on a cell. The monoclonal antibody therapy targets the molecule and attaches to the cell, causing the cell to die. Most chemotherapy affects normal tissue cells as well as CLL cells. Monoclonal antibody therapy may affect some normal lymphocytes but spare most other cells. Even though the infusion of a monoclonal antibody into a patient’s vein may cause a short period of fever, chills or low blood pressure, generally people experience less troubling side effects with monoclonal antibody therapy than with chemotherapy.

The monoclonal antibody therapies rituximab (Rituxan®) and alemtuzumab (Campath®) are used to treat people with CLL. Rituximab targets CD20 on the CLL cell’s surface; alemtuzumab targets CD52. Alemtuzumab is approved as a single agent for CLL treatment. Both rituximab and alemtuzumab have been very effective in treating many people with CLL.

These therapies continue to be studied in clinical trials. Other new monoclonal antibodies, such as ofatumumab (Arzerra®) and lumiliximab are also being studied in clinical trials, either alone or combined with chemotherapy, as treatment for previously untreated patients and for patients with refractory or relapsed CLL.

Stem-cell Transplantation

Patients with CLL may be candidates for stem-cell transplantation. In stem-cell transplantation, immature blood cells (stem cells) are taken from the blood or bone marrow of the patient (autologous transplantation) or a compatible donor (allogeneic transplantation). Stem-cell transplantation is an aggressive treatment that is still considered experimental but may be an option for younger CLL patients who no longer respond to treatment.

Radiation Therapy

Radiation therapy may be used:

  • To reduce the size of an enlarged spleen (rarely used)
  • To reduce the size of a specific lymph node.


Surgery to remove an enlarged spleen is rarely necessary but can be done:

  • To relieve the pressure caused by the enlarged spleen on other organs
  • To stop the increased destruction of red blood cells and platelets.


Relapsed or Refractory CLL

“Relapsed CLL” is the term for disease that responded to therapy but, after six or more months, stopped responding. “Refractory disease” is the term for CLL that does not result in a remission (but may be stable) or disease that gets worse within six months of the last treatment.

People who are treated for relapsed or refractory CLL often have good quality years of remission after more treatment. Treatment guidelines for people with relapsed CLL are generally the same as treatment for newly diagnosed people.

People who have refractory CLL with a short time to progression after the first treatment and/or CLL cells with del 17p often do not respond to standard chemotherapy. These people are advised to speak to their physicians about whether or not treatment in a clinical trial is a good option for them. Investigative clinical protocols for drug therapies or allogeneic stem-cell transplantation may offer appropriate treatment options.