Treatment options for people with CLL vary greatly, depending on the disease stage (risk group) and if the leukemia is causing any symptoms. Because CLL generally can't be cured 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) is one factor when looking at treatment options. Newer tests that look at chromosome changes and molecular markers (such as ZAP-70 and CD38) also offer important information about a patient's outlook. These tests are just starting to be included when looking at treatment options.

Low-risk CLL

The prognosis (outlook) for this group is often very good, with long survival expected. Most patients can be observed with careful and frequent follow-up exams. Treatment should be considered if there are signs that the leukemia is progressing or if the patient develops bothersome symptoms. When needed, initial treatment is usually chemotherapy, as described in the next section.

Intermediate- and High-risk CLL

Patients with intermediate- and high-risk CLL who do not have any symptoms may not need treatment right away. They can often be observed for signs of progression and onset of new symptoms.

When treatment is needed there are several options, although it's not yet clear which might be best. 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.

While 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 rituximab or alemtuzumab (Campath) as part of first-line therapy. It's not yet clear how effective they might be on their own, but they are often used along with other drugs.

Other combinations of drugs may also be also used. 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.

If very high numbers of leukemia cells are causing 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. In this procedure, 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.

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, while older people may 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 wasn't long-lasting, using the same treatment again may not 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.

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 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 other blood 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 CLL alters a patient's immune system in a way that causes it to attack his or her own red blood cells (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, but these cases are often hard to treat.

Less often, CLL may transform to prolymphocytic leukemia (PLL). 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.

Acute myeloid leukemia (AML) is another rare complication in patients who have been treated for CLL. Drugs such as chlorambucil 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.