Treatment

The treatment of CLL depends on the patient’s stage, risk status, and overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan.

Because CLL often develops slowly, many people may not require treatment right away, and some may never require treatment at all. Although the available treatments can be highly effective, none of the standard therapies is capable of eliminating all of the CLL, and patients are not cured of their disease with treatment.

This section outlines treatments that are the standard of care (the best treatments available) for this specific type of cancer. Patients are also encouraged to consider clinical trials as a treatment option when making treatment plan decisions. A clinical trial is a research study to test a new treatment to prove it is safe, effective, and possibly better than standard treatment. Your doctor can help you review all treatment options. For more information, visit the Clinical Trials section.

Descriptions of the most common treatment options for CLL are listed below.

Watch and wait, for early-stage CLL

For some patients, symptoms and/or the presence of large amounts of CLL in the blood, lymph nodes, or spleen require treatment shortly after the diagnosis is made. In other patients, however, it is possible and recommended for doctors to monitor the patient without active treatment. During this time, the patient’s blood counts are monitored and physical examinations are performed on a regular basis. If the CLL shows signs of worsening, active treatment would then begin. Multiple studies have shown that no harm comes from the watch-and-wait approach (also called active surveillance), as compared with immediate treatment of patients with early-stage CLL. Some patients remain without symptoms for years, or even decades, and will not need any treatment.

Treatment is recommended for patients who develop symptoms and/or worsening blood counts. These might include increasing fatigue, night sweats, enlarging lymph nodes, or falling red blood cell or platelet counts. People with CLL are encouraged to talk with their doctor about whether their symptoms require treatment, balancing the benefits of treatment with side effects that may result. Find out more about starting cancer treatment.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. In systemic chemotherapy, the drugs travel through the bloodstream to cancer cells throughout the body. Chemotherapy is given by a medical oncologist, a doctor who specializes in treating cancer with medication, or a hematologist, a doctor who specializes in treating blood diseases. Some people may receive chemotherapy in their doctor's office; others may go to the hospital. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a specific time.

When treatment begins, doctors may use a number of different drugs depending on the stage of the disease and the person’s age and health. Chemotherapy may be given in pill form and taken orally (by mouth), by intravenous (IV) infusion, or by subcutaneous (SQ) injection (an injection under the skin). Sometimes, a doctor may use a combination of drugs, but a combination of drugs is not always better than a single drug.

One of the first drugs people with CLL may receive is called fludarabine (Fludara). Fludarabine belongs to a class of drugs called nucleoside analogues. Other nucleoside analogues, including pentostatin (Nipent) and cladribine (Leustatin), are also sometimes used to treat patients with CLL, although fludarabine is used most commonly.

Chlorambucil (Leukeran) and cyclophosphamide (Cytoxan or Neosar) belong to a class of drugs called alkylating agents. Both drugs can be given orally, while cyclophosphamide can also be administered intravenously. Cyclophosphamide may be given alone or with prednisone (available under many brand names), a type of oral corticosteroid.

In the past, patients were initially treated with either fludarabine alone or chlorambucil/prednisone, switching to the alternative regimen if the initial treatment did not work well. Today, these drugs are often administered together, with combinations including rituximab (Rituxan) (see below) and fludarabine; cyclophosphamide and fludarabine; cyclophosphamide, fludarabine and rituximab; or pentostatin, cyclophosphamide, and rituximab. The choice of therapy often depends on the patient’s age, general health, and the interest in and availability of clinical trials. Other drugs, including alvocidib (sometimes called flavopiridol), bendamustine (Treanda), and lenalidomide (Revlimid) are being evaluated for treating CLL.

Learn more about chemotherapy and preparing for treatment. The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions by using searchable drug databases.

Monoclonal antibody therapy

Rituximab is a monoclonal (synthetic) antibody that is given intravenously and binds to a protein on the surface of B cells, killing some of the CLL cells and potentially increasing the effect of chemotherapy. As mentioned above, rituximab is currently being evaluated in combination with chemotherapy.

Alemtuzumab (Campath-1H) is another monoclonal antibody that has been approved by the U.S. Food and Drug Administration (FDA) for use with advanced CLL that is no longer responding to other treatments. It can be used in both T-cell and B-cell CLL. This antibody can be given either intravenously or as a subcutaneous (under the skin) injection.

Side effects from chemotherapy/monoclonal antibody therapy

Chemotherapy for CLL may be associated with nausea and vomiting, although nausea and vomiting can generally be prevented with drugs. Doctors will also closely watch for decreases in normal blood counts, which can lead to an increased risk of infection (due to decreased neutrophils), bleeding (due to decreased platelets), and fatigue (due to anemia). To manage these side effects, some patients need transfusions of red blood cells and platelets or antibiotics to treat infections.

Decreases in blood counts following chemotherapy are sometimes more severe in people with CLL than in other types of cancer because of the presence of CLL cells in the bone marrow. Patients are encouraged to ask their doctors about the symptoms they might experience, how such complications might be prevented, and how closely they should be monitored.

Sometimes, subcutaneous injections of white blood cell growth factors such as filgrastim (Neupogen), sargramostim (Leukine), or pegylated filgrastim (Neulasta) are used to increase the bone marrow production of normal white blood cells. Injections of epoetin (Procrit or Epogen) or darbepoetin (Aranesp) can be given to increase red blood cell production. Read more about ASCO’s recommendations for white blood cell growth factors and epoetin and darbepoetin treatment.

The initial infusions of rituximab and alemtuzumab are often accompanied by fevers and chills, which usually disappear after the first few treatments.

One of the side effects of both CLL and its treatment is the risk of developing a bacterial, viral, or fungal infection. Doctors may call these opportunistic infections because these infectious agents take advantage of a weak immune system. In particular, patients with CLL often develop infections with herpes viruses, either in the form of cold sores or as herpes zoster (shingles). Herpes zoster can become quite painful and progress to a severe infection. Patients should inform their doctors immediately if they notice a rash or skin eruptions resembling hives that are often grouped together and form the appearance of a band across the chest or abdomen, or extend down the legs, arms, or face. These infections can be treated effectively with antiviral drugs, with better results when treated early.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. Radiation therapy is not used frequently in people with CLL because the disease is located throughout the body. However, radiation therapy can be very helpful in shrinking an enlarged spleen or swollen lymph nodes and eliminating symptoms that may be associated with such growths.

Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished. Learn more about radiation therapy.

Remission

The goal of treatment is to eliminate any symptoms associated with the CLL and to reduce the amount of remaining CLL as much as possible. A complete remission (CR) occurs when the doctor cannot find any evidence of cancer remaining after repeated testing. A partial remission (PR) is when there is some cancer remaining; this is the most common outcome following current methods of treatment of CLL. With a PR, patients can feel quite well with normal blood counts, have no swollen lymph nodes or spleen, but still have considerable amounts of CLL remaining as can be detected by examination of the bone marrow biopsy with a microscope.

The goal of newer, more intensive treatments is to produce much greater decreases in the levels of cancer cells in the hope of prolonging survival. In the future, the definition of a CR in CLL is likely to change with advances in technology. For example, some sensitive tests can now detect extremely small levels of the abnormal DNA characteristic of CLL. This measurement is called a molecular remission.

Refractory and recurrent CLL

If the leukemia has not responded to the initial treatment, the disease is referred to as refractory CLL. Because CLL cannot be reliably cured using currently available standard therapies, CLL generally comes back after treatment, called recurrent CLL. The length of response can vary from weeks to many years, and the pace of regrowth of the disease can vary considerably. Detection of recurrence does not mean that treatment is needed immediately, and a period of observation (watch-and-wait approach) is usually advisable, with treatment offered if the disease begins to cause symptoms again. If CLL becomes resistant to one drug, treatment with other types of drugs is recommended.

Some symptoms can be treated with other approaches, examples of which include radiation treatment or a splenectomy (surgery to remove an enlarged spleen). Some patients who experience recurrent infections may benefit from monthly intravenous infusions of immunoglobulin because patients with CLL have reduced amounts of normal antibodies. Patients who develop antibodies that destroy their own blood cells (see above) are often treated with high doses of corticosteroids to reverse this process.

Stem cell transplantation/bone marrow transplantation

A stem cell transplant is a medical procedure in which diseased bone marrow is replaced by highly specialized cells, called hematopoietic stem cells. Hematopoietic stem cells are found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because blood stem cells are typically what is being transplanted, not the actual bone marrow tissue.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO). ALLO is the type of transplant typically used for treating CLL.

In an ALLO transplant, stem cells are obtained from a donor whose tissue matches the patient’s on a genetic level; this testing is called HLA-typing. Most often, a patient’s brother or sister serves as the donor, although unrelated donors can serve as the donor too. Millions of people worldwide have volunteered to donate stem cells for patients who do not have matched family members; your health care team will search a computer registry to look for a match. In addition, a donation of stem cells derived from umbilical cord blood is sometimes considered if family donors are not available. An ALLO transplantation is a consideration is selected younger patients with CLL that has not responded to treatment with chemotherapy and immunotherapy who are in otherwise good overall health.

In an AUTO transplant, the patient’s own stem cells are used. The stem cells are obtained from the patient when he or she is in remission from previous treatment. The stem cells are then frozen until they are needed, usually after the high-dose treatment (explained below) is completed. AUTO transplants are usually not done in patients with CLL.

In both types, the goal of transplantation is to destroy cancer cells in the marrow, blood, and other parts of the body and have replacement blood stem cells create healthy bone marrow. In most stem cell transplants, the patient is treated with high doses of chemotherapy and/or radiation therapy to destroy as many cancer cells as possible. This also destroys the patient’s bone marrow tissue and suppresses the patient’s immune system so that, in an ALLO transplant, the donor cells are not rejected by the body. After the high-dose treatment is given, blood stem cells are infused into the patient’s vein to replace the bone marrow and restore normal blood counts from donor cells. Sometimes, ALLO transplants can also be performed after giving lower doses of chemotherapy and/or radiation therapy that are still sufficient to suppress the immune system and allow growth of the donor cells. (These transplants, sometimes termed “mini-transplants” or “reduced intensity transplants” have less immediate side effects, allowing the procedure to be used for older patients.)

Before recommending transplantation, doctors will talk with the patient about the risks of this treatment and consider several other factors, such as the type of cancer, results of any previous treatment, and patient’s age and general health.

For both ALLO and AUTO transplant types, the replacement cells engraft (begin to make new blood cells) and turn into healthy, blood-producing tissue in 10 days to three weeks. Destroying the patient’s own marrow reduces the body’s natural defenses, temporarily leaving the patient at an increased risk of infection. Until the patient’s immune system is back to normal, patients may need antibiotics and blood transfusions.

In an ALLO transplant, another major risk is that the donor’s cells will recognize the patient’s body as foreign, causing graft-versus-host disease (GVHD). GVHD may be a serious complication of allogeneic transplants and can be fatal. Other side effects may include liver problems, diarrhea, infections, and rashes. However, GVHD can also be a benefit, in that the donor cells can recognize the cancer cells as foreign and destroy these cells, a mechanism that is one of the major reasons why ALLO transplantation generally works so well over the long term. The risk of GVHD can be reduced with exact HLA-type matching and the use of preventive drugs.

Learn more about bone marrow and stem cell transplantation.

Find out more about common terms used during cancer treatment.