Treatment options for people with CLL vary greatly, depending on the disease risk group and if the leukemia is causing any symptoms. While many people live a long time with CLL, in general it is very difficult to cure, and early treatment hasn't been shown to change the outcome of the disease. Because of this and because treatment can cause side effects, doctors often advise waiting until the disease is progressing or symptoms appear before starting treatment.

The risk group, based on the Rai staging system (see "How is chronic lymphocytic leukemia staged?"), is one factor when looking at treatment options. A person's age, general health, and other prognostic factors are important as well. Newer lab tests that look at chromosome changes and molecular markers may also offer important information about a patient's outlook. For example, people whose CLL cells have chromosome 17 deletions or high levels of ZAP-70 and CD38 are more likely to have faster growing forms of CLL and may need to be treated more aggressively. Tests for these changes are just starting to be included when looking at treatment options.

Low-risk CLL

People in this group are often diagnosed based on a high lymphocyte count in the blood but otherwise have normal blood counts and do not have enlarged lymph nodes or organs. The prognosis (outlook) for people in this group is often very good, with long survival expected.

Most people can be observed with careful and frequent follow-up exams. Treatment is considered if there are signs that the leukemia is progressing or if a person develops bothersome symptoms. When needed, initial treatment is usually chemotherapy, as described in the next section.

Intermediate- and high-risk CLL

Some patients with intermediate-risk CLL (stages I and II) may not have any symptoms and might not need treatment right away. They can often be watched for signs of disease progression and the start of new symptoms. Patients with high-risk CLL (stages III and IV) are more likely to need immediate treatment.

When treatment is needed there are several options. Most doctors use fludarabine as the first treatment, particularly in younger people. It may be given along with an alkylating agent (cyclophosphamide or chlorambucil), with the monoclonal antibody rituximab (Rituxan), or as a combination of all 3 drugs.

Although fludarabine is very active against CLL, it can have side effects such as increasing the risk of infections. For people who may have trouble with side effects, such as older people or those with other health problems, an alkylating agent (chlorambucil or cyclophosphamide) may be used instead, either alone or with a steroid drug (such as prednisone).

Doctors are now studying the use of the monoclonal antibodies such as rituximab, ofatumumab (Arzerra), or alemtuzumab (Campath) as part of first-line therapy, either alone or along with other drugs.

Other drugs or combinations of drugs may also be also used. For example, bendamustine is a newer drug with properties of both alkylating agents and purine analogs. Doctors are now trying to determine where it fits in the first-line treatment of CLL. Some doctors combine cyclophosphamide with other drugs such as vincristine and prednisone. This combination is known as the CVP regimen. If doxorubicin is also included, it is known as the CHOP regimen.

If the only problem is an enlarged spleen or swollen lymph nodes in one region of the body, localized treatment with low-dose radiation therapy may be used. Splenectomy (surgery to remove the spleen) is another option if the enlarged spleen is causing symptoms.

Some people who have very high-risk disease may be best treated early with some type of stem cell transplant (SCT). Because it's still not clear how effective this treatment is for CLL, most stem cell transplants are done as part of a clinical trial. Younger people may be eligible for an autologous or allogeneic SCT. Some older people who may not be able to tolerate such transplants may still be eligible for a non-myeloablative transplant (mini-transplant).

Second-line treatment of CLL

If the initial treatment is no longer working or the disease comes back, another type of treatment may help. If the initial response to treatment lasted a long time (usually at least a few years), the same treatment can often be used again. If the initial response wasn't long-lasting, using the same treatment again isn't as likely to be helpful. The options will depend on what the first-line treatment was and how well it worked, as well as the person's health.

Many of the drugs and combinations listed above may be options as second-line treatments. For many people who have already had fludarabine, alemtuzumab seems to be helpful as second-line treatment, although it carries an increased risk of infections. Other purine analog drugs, such as pentostatin or cladribine (2-CdA), may also be tried. Ofatumumab may be another option if other second-line treatments are no longer working.

Some people may have a good response to first-line treatment (such as fludarabine) but may still have some evidence of a small number of leukemia cells in the blood, bone marrow, or lymph nodes. This is known as minimal residual disease. Because CLL can't be cured, doctors aren't sure if further treatment right away will be helpful. Some small studies have shown that alemtuzumab can sometimes help get rid of these remaining cells, but it's not yet clear if this improves survival.

Treatment of complications of CLL

CLL can cause serious problems with the blood and some of its components. It can also (rarely) transform into another, more aggressive type of cancer. Treatment of CLL itself may also lead to the development of another cancer.

Sometimes very high numbers of leukemia cells in the blood cause problems with normal circulation. Chemotherapy may not lower the number of cells until a few days after the first dose. In the meantime, leukapheresis may be used before chemotherapy. For this procedure, a needle is placed into a vein in the arm. The patient's blood is passed through a special machine that removes white blood cells (including leukemia cells) and returns the rest of the blood cells and plasma to the patient. This treatment lowers blood counts right away. The effect is only for a short time, but it may help until the chemotherapy has a chance to work.

People with CLL often have weakened immune systems and are at high risk for certain kinds of infections. Doctors may suggest vaccines to prevent some of these infections. Finding and treating infections early is an important part of follow-up for people with CLL, even in those who aren't getting treatment with chemotherapy.

Sometimes CLL alters a patient's immune system in a way that causes it to attack his or her own red blood cells (called auto-immune hemolytic anemia) or blood platelets (immune-mediated thrombocytopenia). These conditions are treated with drugs that weaken the immune response. Steroids such as prednisone are often helpful, as are other drugs such as cyclosporine. Monoclonal antibodies like rituximab can also help in some cases.

One of the most serious complications of CLL is a change (transformation) of the leukemia to a high-grade or aggressive type of non-Hodgkin lymphoma called diffuse large cell lymphoma. This happens in about 5% of CLL cases, and is known as Richter syndrome. Treatment is often the same as it would be for lymphoma (see the American Cancer Society document, Non-Hodgkin Lymphoma for more information), but these cases are often hard to treat.

Less often, CLL may transform to prolymphocytic leukemia. As with Richter syndrome, these cases can be hard to treat. Some studies have suggested that certain drugs such as cladribine (2-CdA) and alemtuzumab may be helpful.

In rare cases, patients with CLL may have their leukemia transform into acute lymphocytic leukemia (ALL). If this happens, treatment is likely to be similar to that used for patients with ALL (see the American Cancer Society document, Leukemia -- Acute Lymphocytic).

Acute myeloid leukemia (AML) is another rare complication in patients who have been treated for CLL. Drugs such as chlorambucil can damage the DNA of blood-forming cells. These damaged cells may go on to become cancerous, leading to AML, which is very aggressive and often hard to treat (see the American Cancer Society document, Leukemia -- Acute Myeloid).

Last Medical Review: 07/27/2009
Last Revised: 07/27/2009