CLL watchful waiting: When is treatment necessary?

December 4, 2025

For many people newly diagnosed with chronic lymphocytic leukemia (CLL), the first recommendation isn’t always treatment, it’s watchful waiting. This approach can feel unsettling when you’ve just learned you have cancer, but for CLL, it’s often the first step. Dr. Bita Fakhri, a CLL/small lymphocytic lymphoma (SLL) expert at Stanford University, explains the guiding principle in slow-growing leukemias is straightforward: treatment should never be more toxic than the disease itself.

Watchful waiting means your care team monitors your CLL closely, even though treatment hasn’t started. Guidelines from the International Workshop on CLL (IWCLL) set clear criteria for when treatment should begin, so until those criteria are met, starting therapy early doesn’t improve outcomes and can introduce unnecessary side effects.

This period isn’t passive. Dr. Fakhri shares what symptoms to look for to help you stay proactive during this time.

Symptoms to look out for during watchful waiting with CLL

Dr. Fakhri outlines several categories of symptoms that can signal it’s time to move from monitoring to treatment.

1) B symptoms

B symptoms are signs that your disease is becoming more active. They include:

Unexplained, persistent fevers
Drenching night sweats—the kind that require changing clothes or sheets
Unintentional weight loss of 10% or more over 6 months
Severe fatigue that can’t be explained by thyroid changes, vitamin deficiencies, or other common causes

These symptoms matter because they reflect systemic inflammation driven by CLL.

2) Compressive or constitutional symptoms

CLL can cause lymph nodes or organs to enlarge. When that enlargement starts to affect your daily life, it’s a sign that treatment may be needed.

These symptoms may look like:

Swollen lymph nodes in the neck, underarms, chest, abdomen, or groin that cause discomfort, pressure, or physical limitations
Shortness of breath or reduced activity tolerance when chest nodes enlarge
Abdominal fullness or early satiety as the spleen grows
Leg swelling or even blood clots, which can happen if groin nodes block lymphatic flow

3) Rapid progression of disease

Dr. Fakhri also shares that your care team watches for signs that CLL is changing quickly.

Clues include:

Lymph nodes that grow rapidly, for example doubling in size over a few months
A quickly enlarging spleen
Falling blood counts, especially hemoglobin and platelets, which can indicate that CLL cells are crowding out healthy bone marrow

A rising absolute lymphocyte count (ALC) can also signal increased activity, but it’s assessed along with other clinical changes to understand the whole picture.

4) Autoimmune complications

Sometimes, CLL triggers the immune system to attack healthy red blood cells. Dr. Fakhri explains, “There is a phenomenon called Evans syndrome in patients with CLL. That’s when the clone has a tendency to produce autoimmune antibodies, and these autoimmune antibodies attack healthy tissues. Your marrow is producing healthy red blood cells, but your CLL is producing antibodies that attack red cells.”

In these situations, people may suddenly present with very low hemoglobin or platelets, even when the bone marrow itself is functioning normally. These complications usually prompt treatment.

How often will you check in with your doctor?

Monitoring frequency depends on the biology of your CLL. Your CLL FISH panel and IGHV mutation status give important clues about the pace of the disease.

For example, people with deletion 13q and mutated IGHV often have a very slow-moving form of CLL. Dr. Fakhri shares that she typically sees these patients every six months. On the other hand, those with higher-risk markers, such as unmutated IGHV or deletion 17p, may be monitored every three months, even if they feel well, to better understand the disease’s progression.

The goal is to “not turn watch and wait into watch and worry.” “There is no reason for you to go into our labs every month,” she continues. “I think every 3 months is good enough, as long as you feel like yourself. It’s different if all of a sudden you’re having all those symptoms, but without symptoms, every 3-6 months.”

Living well during watchful waiting

While you may not need treatment yet, staying healthy now can make a meaningful difference later. Dr. Fakhri says, “When the time comes that you need treatment for CLL, the better your performance status, the easier these treatments are probably going to be on you.”

Dr. Fakhri encourages focusing on exercise, which helps lower inflammation, and choosing a diet centered on fruits, vegetables, nuts, whole grains, and healthy fats like olive oil or avocado.

She also emphasizes moderation over restriction. “White meat in general is better than red meat, but what good is life if you’re not living it? If you like your steak, just enjoy everything in moderation.”

The bottom line

Watchful waiting is a safe, research-backed approach that protects patients from treatment they don’t yet need while ensuring care begins at the right time. And the landscape of CLL has never been more hopeful. As Dr. Fakhri notes, “there is never a good time to have CLL, but there is no better time than now,” thanks to significant advancements in therapy and supportive care.

If symptoms change, new discomforts appear, or something doesn’t feel right, reach out to your care team. During watchful waiting, your symptoms are one of the most important guides to when treatment should begin.