Active Surveillance For Chronic Lymphocytic Leukemia (CLL)

"I usually tell [my patients] that after their diagnosis, I want them to leave my office and forget that they have it. Then they come back in 6 months, I have to remind them that they have it," says Dr. Marc Hoffmann, Medical Director of Lymphoma and Myeloma at the University of Kansas Cancer Center. He continues, "That's, of course, not the way it works. People naturally have anxiety about things."

Still, active surveillance or a watch-and-wait approach should not turn into "watch and worry." Active surveillance requires much monitoring, including regular physician visits, laboratory work, and maintenance care.

What is Chronic Lymphocytic Leukemia?

RELATED: Chronic Lymphocytic Leukemia (CLL): Overview

CLL starts within the bone marrow, which is the red, spongy tissue that lines the hollow insides of long bones, such as hip and leg bones. Bone marrow produces many essential blood cells, such as red blood cells (RBCs), white blood cells (WBCs) or lymphocytes, and platelets.

Blood cancers can affect any of these cell lines. When cancers rev up the production of WBC, they are called termed leukemias or lymphomas. Leukemias and lymphomas signify the location of the involved cancer cells. In leukemia, the cancer cells occupy the bone marrow and the blood. In lymphoma, the errant cells take up residence within the lymph nodes and the lymphatic system. They can often form masses that can be seen or felt in lymphoma patients.

CLL signals an abnormal number of WBCs or lymphocytes within the bone marrow and blood. Despite increased numbers, these leukemic WBCs are abnormal and lack the ability to fight infections. Furthermore, as their number increases, they crowd out the bone marrow leaving little room to produce normal RBCs, WBCs, and platelets. This can lead to anemia (lack of RBCs), a vulnerability to infections (lack of WBCs), and an elevated risk of bleeding and bruising (lack of platelets), even after minor injuries.

RELATED: The Exact Cause of CLL is Hard to Know

CLL is the most common leukemia in older adults. An average patient is diagnosed around age 70. It is rare in people younger than 40 and even rarer in children. According to the American Cancer Society, around 59,610 new cases of leukemia will be diagnosed in the United States in 2023. One quarter or almost 18,000 of these will be CLL. This disease will also result in 4,490 deaths within the same year.

RELATED: Getting a Second Opinion is a Smart Move After a CLL Diagnosis

Why Consider Active Surveillance for CLL?

CLL patients can live for years without any symptoms or needing treatment. In fact, a small number of these patients, such as those with del13q14 but no other genetic mutations, may enjoy the same life expectancy without any treatment as those who do not have CLL.

But CLL is still "cancer" and patients can be understandably wary of sitting back and waiting for their cancer to become bad enough to warrant treatment. Yet physicians need to educate them about the fact that early treatment may carry unjustifiable risks. Here are some key factors to consider:

• There has been no robust scientific evidence to date that early treatment for people with early, low-risk CLL holds any tangible benefit for or prolongs the lifespan of patients. It can be hard to justify a medical treatment that does not carry at least some amount of benefit especially when it entails real risks and side effects.
• Chemotherapies have significant side effects, such as nausea, vomiting, diarrhea, weight loss, and hair loss, which can be devastating for patients. Targeted therapies have their own downsides, such as fatigue, rashes, muscle cramps, and muscle and bone pains. Immunotherapies carry many risks, from causing mild flu-like symptoms to a full-blown autoimmune inflammation of the lungs, kidneys, and heart. These risks must be carefully weighed against potential benefits while considering treatment.
• If treated early, some CLL patients may develop resistance to the drugs they receive over time. This can become especially problematic when patients actually need treatment at a later stage of their disease but can no longer use any of those drugs.

What Will be Monitored During Active Surveillance?

"These are maintenance things that need to be done [for CLL patients]," says Dr. Hoffmann. He continues, "when I see patients, even if they do not have any indication for treatment, we are making sure they are doing everything else they need to be doing."

During active surveillance, physicians particularly need to manage the following aspects of CLL:

Increased risk of infections

The abnormal WBCs produced in CLL are unable to fight off infections. Thus, the immune systems of CLL patients are compromised (immunocompromised). This can make them especially susceptible and vulnerable to everyday infections, as detailed below. Notably, CLL patients should never receive live vaccines given their compromised ability to fend off pathogens.

• Influenza and Pneumonia: Patients should receive yearly influenza vaccination as well as pneumococcal pneumonia vaccination every 5 years.
• Shingles: It is more common and usually more severe in the immunocompromised CLL population. Shingrix ® vaccine, an inactivated vaccine for shingles, is safe for CLL patients and can be given to them any time after they turn 18 years old. They should not be given Zostavax, which is a live vaccine.
• Deadly Fungal and Bacterial Infections: These infections can be particularly serious in the CLL population, In fact, one-third of all deaths in CLL patients may be due to deadly infections. Physicians should monitor their patients for their risk of such infections, and diligently treat them with antibiotics should they develop them. Patients who are prone to recurrent infections may require regular preemptive treatment with injections of immunoglobulins to make up for their immune deficiency.
• Cytomegalovirus (CMV) and Hepatitis B Virus (HBV): CMV and HBV infections have been reported in CLL patients, although they are usually associated with patients who are actively receiving or have failed their treatments. However, given this risk, physicians could consider monitoring their patients for these viruses through regular testing.

"I need to make sure they are up to date on their vaccinations. A lot of the time, I will take over the management of infections in their cases. Sometimes, they need to be on some sort of prophylaxis to help prevent them from getting infections," relates Dr. Hoffmann.

Second Cancers

Immunosuppression can put CLL patients at an increased risk for developing second cancers compared to the average population. Thus, they need to be prompt and diligent about cancer screenings.

Cancers that are most frequently seen in CLL patients include skin cancers (usually not melanomas, although melanomas may also occur), breast cancer, lung cancers, other blood cancers such as acute myeloid leukemias, prostate cancer, kidney and bladder cancers, and cancers of the head and neck.

"By far, the most common type of second cancers [in CLL patients] are skin cancers," says Dr. Hoffmann. "The majority of them are non-melanoma skin cancers, either basal cell or squamous cell cancers… thus, [patients] need to get a skin check [by a dermatologist] every year."

Questions to ask your doctor?

• What will my follow-up plan, including monitoring, vaccinations, and cancer screenings, look like if I undergo active surveillance?
• What will you monitor during my follow-up visits? Physical examination? Blood work?
• What should I keep an eye on, in terms of signs and symptoms of CLL, in between my appointments?
• Can I change my mind and switch to treatment while undergoing active surveillance?

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