Chronic Lymphocytic Leukemia (CLL) - Treatment Options and Prognosis

Waiting, Chemotherapy, Monoclonal Antibodies, or Stem Cell Transplants for CLL

How is chronic lymphocytic leukemia (CLL) treated?. Photo©Wavebreakmedia

What are the best treatments for chronic lymphocytic leukemia (CLL)?

Review of Chronic Lymphocytic Leukemia (CLL)

If you're familiar with the symptoms and risk factors for CLL, and have gone through the diagnosis and staging of CLL you're probably ready to take the next step.  After all, you've heard plenty about the various treatments available for cancer.

Sadly, at this time there is no therapy that is considered to be a cure for chronic lymphocytic leukemia (CLL).

  But even without a cure, some people can live for years and even decades with the disease. At the current time, treatment is directed toward providing patients with relief from their symptoms, with hopes of ensuring a good quality of life and a prolonged remission. 

Watch and Wait

Patients who are not experiencing any symptoms of CLL, such as night sweats, fevers, weight loss, anemia (a low red blood cell count,) thrombocytopenia (low platelet counts) or frequent infections are not likely to benefit from treatment. Therapy at this stage in the disease will not prolong your life, nor will it slow down the progression of your leukemia. Therefore, a "watch-and-wait" approach is usually taken. In a watch-and-wait situation, you will be followed by a hematologist or oncologist and will need to have blood work and be seen by your specialist every six to 12 months.

In between visits, you will need to pay attention for signs that your cancer may be progressing.

You may notice:

  • Swelling in your lymph nodes
  • Abdominal discomfort or pain
  • Signs of anemia such as pale skin and feeling extremely tired
  • Frequent infections or an infection that just won’t go away
  • Bleeding problems or easy bruising

Many patients can remain on watch and wait for years before requiring treatment for their CLL.

It can be very difficult to learn that you have cancer, then "wait for it to get worse" before you treat it. You may feel like you just want to fight that leukemia and get it over with!

While it may be hard to be patient, it is very important that you understand that watch and wait is the standard when CLL is not showing any symptoms. Research to this point has not shown any benefit to starting treatment early.


For many years, oral chemotherapy with Leukeran (chlorambucil) was the standard of treatment for CLL once the cancer began to progress. While most patients did quite well on this therapy, it did not provide a complete response(CR) very often. These days, chlorambucil is only used in patients who have other health concerns that prevent them from receiving stronger, more toxic chemotherapy.

More recently, Fludara (fludarabine) chemotherapy has been shown to be effective in treating untreated as well as relapsed CLL. It has improved CR and progression-free survival (PFS) rates when compared to chlorambucil, but still has not demonstrated an advantage in overall survival (OS) when used alone.

Another drug from the same family, Nipent (pentostatin,) has also been used as part of CLL therapy.

The real improvement in CLL treatment occurred when Cytoxan (cyclophosphamide) was added in combination with fludarabine therapy. Using this regimen ("FC" or "Flu/Cy"), treatment response was increased as evidenced by CR, PFS, and OS. While combining these two drugs together does cause some increase in toxicity, it does not appear to cause a higher rate of severe infections.

Monoclonal Antibodies

The outcomes in CLL therapy have been further improved by the addition of monoclonal antibody treatment.  Monoclonal antibodies are essentially artificial antibodies that attack a cancer.  Whereas you immune system recognizes abnormal proteins on the surface of a bacteria or virus, these drugs "recognize" abnormal markers on the surface of cancer cells.  The addition of the monoclonal antibody Rituxan (rituximab) to the regimen ("FCR" protocol) has provided people with CLL a response rate of 90% and 96% and a CR of 50% ad 70%.

Another monoclonal antibody, Campath (alemtuzumab) has been approved by the U.S. Food and Drug Administration (FDA) for use in the treatment of CLL. It is targeted toward a different cell surface antigen "marker" than rituximab, and may be used by itself or in combination with chemotherapy.

Stem Cell Transplant

In the case of other types of blood cancers, a great deal of research has been done to compare survival outcomes of patients who receive chemotherapy, against stem cell transplant. Since the average age of a newly diagnosed CLL patient is between 65 and 70 years old, typically too old to be considered a transplant candidate, these types of studies have not been done on this population.

Having said that, 40% of CLL patients are under the age of 60 and 12% are under the age of 50. Stem cell transplant may offer a chance for a cure to younger CLL patients with a poor prognosis.

Allogeneic stem cell transplant (transplant using donor stem cells) uses extremely high doses of chemotherapy to treat leukemia and donated stem cells to repopulate the patient’s immune system. The advantage to a allogeneic stem cell transplant is that while it may be more toxic, it can cause a "graft-versus-leukemia" effect. That is, the donated stem cells recognize the leukemia cells as abnormal and attack them.

Even though these techniques are improving dramatically, there are still some major complications in 15 to 25% of patients, one being graft vs host disease in which the donor tissue recognizes that patients own cells as foreign and launches an attack.

Because of the toxic side effects of allogeneic stem cell transplant, they are not shown to improve outcomes in elderly patients.

Currently, research to determine the role of non- myeloablative, or "mini" transplants in CLL is underway. Non-myeloablative transplants rely less on the toxicity of chemotherapy and more on the "graft-versus-leukemia" effect to treat cancer. This type of therapy may provide a treatment option for older individuals who would not be able to tolerate a standard allogeneic transplant.

Autologous stem cell transplants in the treatment of CLL have shown poor results and a high rate of disease relapse, sometimes even years after transplant. While it may have decreased toxicity, autologous transplant is no more effective at treating CLL than non-myeloablative therapy. As a result, autologous transplant is not typically recommended for CLL patients.

Radiation Therapy

In patients with CLL , the use of radiation therapy is limited to providing symptom relief. It can be used to treat areas of swollen lymph nodes that cause discomfort or interfere with movement or function of nearby organs.


For patients who are experiencing an enlarged spleen as a result of the accumulation of CLL cells, splenectomy, or surgical removal of the spleen, may initially help to improve blood counts and relieve some discomfort. As with radiation therapy, splenectomy is used to help control symptoms of the disease and does not provide a cure for leukemia.

Summing it Up

At this time, while treatment for CLL may be able to provide patients with symptom relief and control of their leukemia, it can not provide a cure, and the course of the disease is extremely variable between different people.  However, our understanding of this unique type of leukemia is constantly expanding. The use, for example, of stem cell transplants for people with CLL improved dramatically in the period between 2006 and 2016. Research studies will continue to progress and potentially provide therapies with longer-term control or cure of CLL.


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