Treatment for CLL

Unlike most cancers, chronic lymphocytic leukemia (CLL) is a long-term condition that may not need to be treated for many years. When it is time for treatment, physicians have more options today than ever before to control the disease or put it into remission. 

Small lymphocytic lymphoma (SLL) is closely related to CLL. In SLL, cancer cells are found in the lymph nodes and spleen. In CLL, cancer cells are found in the blood and bone marrow. Most of the information in this treatment section about CLL also applies to SLL.

Fred Hutchinson Cancer Center is one of just a few treatment centers in the country that provides every kind of standard therapy for CLL and also gives you access to the latest innovations through clinical trials. Our CLL specialists work closely with you, your family and each other to make the best plan for you.

Treatment Plan

CLL treatment is highly customized for each patient’s needs.

How Do We Create Your Treatment Plan?

Your Fred Hutch hematologist-oncologist works with an entire group of doctors who specialize in lymphoid cancers like CLL. They include other hematologist-oncologists, radiation oncologists, bone marrow transplant specialists and researchers who are all looking for better ways to treat this disease.

Every week, this team meets in one room. The meeting is called a tumor board. Together, dozens of team members discuss their patients’ treatment plans. This approach means each patient benefits from the experience of the whole group.

The Fred Hutch experts at these meetings, including your physician, will:

  • Talk about if your CLL needs treatment and, if so, when treatment should begin
  • Talk about all possible treatments for your situation
  • Decide which therapies will be most promising for you
  • Check if any clinical trials match your needs, so you can think about joining them

If you have high-risk CLL, we have a dedicated subgroup of providers that focuses on designing your care.

Your care team will walk you and your caregiver through the treatment plan we recommend for you. You will have a chance to share your personal preferences, and you will decide together what happens next.

Why Do Treatment Plans Differ?

The treatment plan we design for you depends on many things, including:

  • Your CLL stage
  • Any chromosome or gene changes in your leukemia cells (like a missing part of a chromosome or having an extra chromosome)
  • If you have a change in the gene IgHV (immunoglobulin heavy-chain variable region gene)
  • If you have symptoms
  • Your age and general health
  • How quickly your leukemia cells grow
  • Your values, needs and preferences, like what type of treatment schedule works in your life and if you want to join a clinical trial

These factors guide decisions about which standard therapies and which clinical trials are the best match for you. 

What is Standard Therapy for CLL?

Treatment for CLL can be very different from person to person. Patients who do not have symptoms or low blood counts are often on watchful waiting. 

If your CLL is getting worse quickly or is higher risk, the standard therapy for most people is targeted therapy or immunotherapy. There are many ways to combine medicines to improve results. Some people with high-risk disease who have already tried other treatments have a blood or marrow transplant.

The goal of active treatment is to put your disease into long-term remission. When you aren’t in remission, the goals are to slow the disease and reduce any symptoms. 

At Fred Hutch, our standard therapy always involves caring for you as a whole person. We help you get relief from side effects and provide many other forms of support, like integrative medicine, nutrition counseling and physical therapy.

Our patients can choose to have promising, new CLL therapies that you can get only through a clinical trial. Many people come to Fred Hutch for access to these studies. Your care team will tell you about studies that might be right for you, so you can think about joining them.

Treatment Process

Some people with CLL can safely wait years, maybe even decades, to begin active treatment. In fact, some never need treatment at all. If you do need active treatment, we choose, combine and schedule your therapies based on what works for CLL like yours. Your care team makes sure you understand each type of treatment and all of your choices.

Watchful Waiting

If your CLL is low or intermediate risk, your physician may recommend watchful waiting. 

This is also called observation or active surveillance. It means you and your physician closely monitor your health for any changes, like signs that your CLL is clearly getting worse.

During watchful waiting, you will visit your doctor for exams and have blood tests on a regular schedule. The schedule depends mainly on your health. We also ask you about your preferences. Some people want to come in more often, especially in the early months after their diagnosis. Then, if their disease is stable, they get comfortable letting more time pass between visits.

In between scheduled visits, you are not on your own. We are here. If you notice health changes, we encourage you to call so we can check if you do need active treatment.

Research shows there is no benefit to starting treatment for CLL early. However, there are benefits to waiting until symptoms begin to bother you, your levels of blood cells get worse or there are other signs that the disease is progressing.

The main benefits of waiting include:

  • You can keep living your life without much of a change. You will not have side effects from treatments you do not need.
  • When you do need treatments later, they will still work just as well.
  • Better options might be available in the future.

Targeted Therapy

Chemotherapy used to be the main treatment for this disease. Now, most people do very well with targeted therapies and immunotherapies. As result, chemotherapy has little to no role.

Targeted therapies work in one of three ways:

  • They target a gene or protein that causes cancer growth.
  • They damage cancer cells directly.
  • They tell your immune system to attack certain cells. This is also called immunotherapy.

Your hematologist-oncologist will prescribe your targeted therapy and set your treatment schedule. Targeted therapies are usually given as a pill that you take at home. Some are given by infusion in repeating cycles. Liquid medicine is put into a vein through an intravenous (IV) line. This can be a line in your arm (peripheral venous catheter) or a port in your chest (central venous catheter). 

You get infusions in a dedicated area of the clinic. Cancer nurses who are experts in infusions will give you these treatments. They will also monitor you during the treatment. They respond to any medical issues that come up and help keep you comfortable.

We have several options that target different features of CLL. Some are used as first-line treatments. Some are saved and used after trying other treatments first. They can be used alone or with other medicines.

Options for Targeted Therapy

Examples of targeted CLL therapies include:

  • Ibrutinib, acalabrutinib and zanubrutinib. They block the enzyme called Bruton’s tyrosine kinase.
  • Venetoclax. It targets CLL with the BCL-2 protein. 
  • Idelalisib and duvelisib. They block the protein PI3K.

Some medicines can be thought of as both immunotherapies and targeted therapies — like rituximab, ofatumumab and obinutuzumab. They target the CD20 protein. 

More targeted therapies are being tested and are available through clinical trials.


For some types of CLL, you may get targeted therapies. These are more exact than standard chemotherapy, which affects all fast-growing cells throughout the body.

Your hematologist-oncologist will prescribe immunotherapies and set your treatment schedule. For CLL, doctors usually use medicines called monoclonal antibodies that target CD20. CD20 is a protein on the surface of some cells, including CLL cells. These medicines include rituximab (Rituxan®), ofatumumab (Arzerra®) and obinutuzumab (Gazyva®). These drugs are often used along with other novel (new) therapeutic agents. 

Researchers at Fred Hutch are also studying cellular immunotherapies, such as CAR T-cell therapy, for CLL. In CAR T-cell therapy, we remove immune cells called T cells from your blood. We genetically modify them to attack cancer cells and then return them to your body. 

Learn more about Immunotherapy

Bone or Marrow Transplant for CLL

A blood or marrow transplant resets your body’s ability to make healthy blood cells. Researchers at Fred Hutch pioneered this form of treatment.

A small number of CLL patients may have a transplant if they have high-risk CLL that does not respond to other targeted treatments or if the disease comes back. 

For CLL, physicians do a transplant using stem cells from a donor. This is called an allogeneic transplant. (For other diseases, they may use the patient’s own stem cells.) First, you get strong chemotherapy to get rid of your CLL. Then the donor’s healthy stem cells restart your body’s ability to make blood cells. Also, white blood cells from the donor may recognize any remaining CLL cells as foreign and attack them. 

A team of Fred Hutch transplant experts will care for you. Your team will include a transplant oncologist, transplant nurse, physician assistant or advanced registered nurse practitioner, pharmacist, registered dietitian, team coordinator and social worker.

Doctors and researchers at Fred Hutch pioneered blood and marrow transplants decades ago. Our researchers continue to improve transplant techniques and to develop new options.

Learn more about Blood and Marrow Transplants

Monitoring Your Health

While you’re in active treatment, your CLL care team will see you regularly for exams and tests to check:

  • How well your treatment is working
  • If there’s any reason to change your treatment
  • If you need help with side effects or supportive care services, like nutrition care or mental health counseling

We update your treatment plan based on the best scientific evidence as well as how your disease responds and what you prefer.

Possible Results of Treatment

Throughout treatment, your care team looks for signs of:

  • Active disease: CLL is still present during or after treatment, or it has come back.
  • Minimal residual disease: Standard tests do not find any CLL cells in your blood or bone marrow. But more sensitive tests do find some cells.
  • Remission: Fewer signs and symptoms of cancer. Partial remission means there are still some signs and symptoms. Complete remission means there are no signs or symptoms.
  • Relapse: The disease, signs or symptoms have come back after they had improved.
  • Refractory disease: The disease does not respond to treatment.

What about “cured”? Sometimes physicians use the word “cured” if cancer has been in complete remission for at least five years. After five years, cancer is less likely to come back (recur), but recurrence is still possible. Doctors do not think of CLL as curable. Instead, the goal is to get lasting remission. 

Managing Side Effects

You might be wondering about possible side effects of treatment, like hair loss or nausea from chemotherapy. If you are, it may be helpful to know that many of today’s treatments are more targeted to cancer cells, so they don’t cause the same side effects as standard chemotherapy. 

You are always at the center of everything we do. CLL physicians, nurses and advanced practice providers are here to help prevent or relieve side effects of treatment.

Get Help with Side Effects

Before you begin treatment, we talk with you about what to expect, based on your treatment plan, and what can help if you do have side effects.

At your appointments, we want you to tell us about any side effects you are having. If you have questions or concerns between appointments, you can call or email us. We will make sure you know how to reach care providers at Fred Hutch after hours, if that is when you need us.

We have many tools to help you feel better, such as:

  • Antibiotics, vaccines and antiviral drugs to prevent or treat infections
  • Transfusions, steroids and medicines that help the immune system to treat low levels of blood cells (low blood counts)
  • Therapy to lower the number of leukemia cells (leukapheresis) to treat circulation problems or to prevent complications that may happen when targeted therapy or chemotherapy breaks down a large number of tumor cells (tumor lysis syndrome)

Coping with Side Effects

Common Side Effects

Side effects are different depending on which treatment you get. They also depend on other things, like how strong your immune system is. These are some of the common side effects of CLL treatment:

  • Unusual tiredness (fatigue)
  • Hair loss
  • Higher risk of infection (due to low levels of white blood cells)
  • Anemia (due to low levels of red blood cells)
  • Easy bruising or bleeding (due to low levels of platelets)
  • Problems in your digestive tract, like sores in your mouth, nausea or vomiting 

Supportive Care Services

Along with treating your CLL, Fred Hutch provides a range of services to support you and your caregiver, before, during and after treatment. This is part of how we take care of you — not just your disease.

From registered dietitians to social workers to spiritual health staff, we have experts who specialize in caring for people with cancer. We understand this may be one of the most intense and challenging experiences you and your family ever go through. We are here to provide the care you need. 

Learn more about Supportive Care

Caregiving During Treatment

If your loved one is getting targeted therapy, immunotherapy or chemotherapy, there are many ways you can help. Caregiving during active treatment for CLL often means doing tasks like these:

  • Keeping track of their appointments and driving them to and from treatment
  • Watching for changes in their condition and telling their care team about any symptoms 
  • Providing physical care, like helping them take medicines
  • Spending time with them and encouraging them
  • Taking care of things at home that they may not be able to do, like grocery shopping and cleaning

Caregiving for Transplant Patients

Caregivers have a special role in blood and marrow transplants. This intense treatment involves chemotherapy (and sometimes radiation) with serious side effects. During the initial recovery period, which often takes at least a month, your loved one will need daily help. We have classes to help transplant caregivers get ready. During recovery, a transplant registered nurse is available by phone 24 hours a day, 7 days a week, to help you.

Continuing Care

When your disease is in remission and you are not on active treatment, it is still important to get follow-up care on a regular basis. At follow-up visits, you will see the same Fred Hutch team who treated your CLL. They will check your overall health and look for signs that your cancer has come back (signs of recurrence).  

Your team will also help with any long-term side effects (which go on after treatment ends) or late effects (which may start after treatment is over).  

For people who had a blood or marrow transplant, the Fred Hutch Long-Term Follow-Up Program provides lifelong monitoring and care. 

Schedule For Follow-up Visits

Just like we personalize your treatment plan for you, we personalize your follow-up schedule, too. Your hematologist-oncologist will base your schedule on many things, including:

  • The features of your CLL
  • Which treatments you had and how your disease responded 
  • How the disease and treatments affected you 
  • How long it has been since your treatment ended

Most patients with CLL are followed for the rest of their life. It is common to have visits more often in the first months and years after active treatment ends and less often as time goes on. This will depend on your exact needs.

What Happens at Follow-up Visits

Follow-up for CLL usually means seeing your hematologist-oncologist for a physical exam and having blood tests to check your blood cell levels. 

If there is any cause for concern, you might have tests to check the health of your bone marrow. Together, you and your physician will go over the benefits and risks of any follow-up options and decide what is right for you.

Meet the CLL Care Team