Treatment options for chronic lymphocytic leukemia (CLL) vary greatly, depending on the person’s age, the disease risk group, and the reason for treating (for example, which symptoms it is causing). Many people live a long time with CLL, but in general it is very difficult to cure, and early treatment hasn't been shown to help people live longer. Because of this and because treatment can cause side effects, doctors often advise waiting until the disease is progressing or bothersome symptoms appear, before starting treatment.
If treatment is needed, factors that should be taken into account include the patient’s age, general health, and prognostic factors such as the presence of chromosome 17 or chromosome 11 deletions or high levels of ZAP-70 and CD38.
Patients who might not be able to tolerate the side effects of strong chemotherapy (chemo) are often treated with chlorambucil alone or with a monoclonal antibody like rituximab (Rituxan) or obinutuzumab (Gazyva). Other options include ibrutinib (Imbruvica), rituximab alone, or a corticosteroid like prednisone.
In stronger and healthier patients, there are many options for treatment. Commonly used treatments include:
- FCR: fludarabine (Fludara), cyclophosphamide (Cytoxan), and rituximab
- Bendamustine (sometimes with rituximab)
- FR: fludarabine and rituximab
- CVP: cyclophosphamide, vincristine, and prednisone (sometimes with rituximab)
- CHOP: cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone
- Chlorambucil combined with prednisone, rituximab, obinutuzumab, or ofatumumab
- PCR: pentostatin (Nipent), cyclophosphamide, and rituximab
- Alemtuzumab (Campath)
- Fludarabine (alone)
- Ibrutinib (alone)
Other drugs or combinations of drugs may also be also used.
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.
Sometimes very high numbers of leukemia cells in the blood cause problems with normal circulation. This is called leukostasis. Chemo may not lower the number of cells until a few days after the first dose, so before the chemo is given, some of the cells may be removed from the blood with a procedure called leukapheresis. This treatment lowers blood counts right away. The effect lasts only for a short time, but it may help until the chemo has a chance to work. Leukapheresis is also sometimes used before chemo if there are very high numbers of leukemia cells (even when they aren’t causing problems) to prevent tumor lysis syndrome (this was discussed in the chemotherapy section).
Some people who have very high-risk disease (based on prognostic factors) may be referred for possible stem cell transplant (SCT) early in treatment.
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 the 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, but it carries an increased risk of infections. Other purine analog drugs, such as pentostatin or cladribine (2-CdA), may also be tried. Newer drugs such as ofatumumab, ibrutinib, idelalisib (Zydelig), and venetoclax (Venclexta) may be other options.
If the leukemia responds, stem cell transplant may be an option for some patients.
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. CLL can't be cured, so 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.
Treating complications of CLL
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 Non-Hodgkin Lymphoma for more information), and may include stem cell transplant, as 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 Leukemia: Acute Lymphocytic).
Acute myeloid leukemia (AML) is another rare complication in patients who have been treated for CLL. Drugs such as chlorambucil and cyclophosphamide 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 Leukemia: Acute Myeloid).
CLL can cause problems with low blood counts and infections. Treatment of these problems is discussed in “Supportive care in chronic lymphocytic leukemia.”
Last Revised: 04/11/2016