If Chronic Lymphocytic Leukemia (CLL) Comes Back

Medically Reviewed by Melinda Ratini, MS, DO on March 31, 2023
4 min read

If you have chronic lymphocytic leukemia (CLL), it's possible that your cancer will come back. The medical term for this is "relapse," and it means your disease returns or grows after you've been without signs of CLL for more than 6 months.

You've got lots of choices when it comes to care after a relapse. You and your doctor will figure out the next steps based on your situation.

You may not need to do anything right away. Your doctor may choose a "watch and wait" approach, especially if you don't have any CLL-related symptoms. They'll keep an eye on your disease through blood work and other tests. That's because there's no evidence that early treatment for low-risk CLL will help you live longer.

When it's time for treatment, your doctor will consider what therapies you've used in the past and how well they've worked. Your overall health, age, and personal treatment goals also matter.

Here are some things your doctor might want you to try:

Targeted therapy. These drugs usually come as a pill you take once or twice a day. They only affect certain proteins in CLL cells. They can block signals that help cancer cells grow and live.

Some drugs that doctors may suggest to treat CLL are:

If you've tried one of these drugs in the recent past, your doctor will probably give you a different one this time. And scientists continue to test new targeted drugs for CLL. You'll likely have even more choices in the future.

Immunotherapy. Monoclonal antibodies are one type of immunotherapy used to treat CLL. They can help your immune system learn to fight off cancer cells. You'll get these drugs through a vein in your arm. They're often used alongside other targeted therapy drugs.

You might take one or more of the following drugs:


In the future, an immunotherapy called CAR T-cell therapy may be available for CLL relapses. That's when a specialist makes genetic changes to your blood in a lab. They add something called chimeric antigen receptor (CAR) to your immune cells, or T cells. They give you these new CAR T cells through a vein in your arm. That helps your body attack cancer cells.

Chemoimmunotherapy (CIT). You may have tried this treatment when you were first diagnosed. It's a mix of immunotherapy and chemotherapy. Chemo drugs help slow the growth of cells all over your body, including cancer cells. You might take them as a pill or a shot.

CIT is something your doctor is more likely to try again if you've been in remission (without signs of cancer) for more than 2 or 3 years.

Some chemo drugs used for relapsed CLL include:

Allogenic stem cell transplant. In this procedure, your doctor will kill off your CLL cells with strong chemotherapy and radiation. Then they give you stem cells from a healthy donor who is your genetic "match." These new stem cells may help you make cancer-free blood.

A stem cell transplant is something your doctor might suggest if other treatments don't work or your CLL comes back in less than 6 months. This treatment tends to work better on younger people who don't have other health problems.

Clinical trials. These are studies that test newer drugs for CLL. You may be able to get a medication that isn't part of standard treatment yet. For more information on clinical trials, you can check the website of the National Institutes of Health.

There are special doctors, nurses, and social workers who can help you feel better throughout treatment. They're part of something called palliative care. Their goal is to help you and your family through all parts of your disease.

You can get help managing lots of things, such as:

  • Pain and tiredness
  • Bruises or bleeding
  • Depression and anxiety
  • Side effects from medicine
  • Deciding your treatment goals

Make a list of topics you want to know more about. Write down your questions before your appointment. That way you don't forget what you want to ask. Here are some ideas to get you started:

  • What happens if I don't treat my CLL?
  • What are all of my treatment options?
  • What are the pros and cons of my treatment choices?
  • What side effects can I expect now and in the future?
  • Can I join a clinical trial?
  • Can I get a referral for palliative care?
  • What happens if my next treatment doesn't work?
  • Will anything cure my disease?