Diagnosing Chronic Lymphocytic Leukemia (CLL) Begins With Blood Work
- Diagnosing chronic lymphocytic leukemia (CLL) relies primarily on blood tests, including a complete blood count (CBC) with a differential and flow cytometry, a specialized test that identifies abnormal B lymphocytes.
- For many people with CLL, blood tests alone provide enough information to make the diagnosis, says Dr. Alan Kerr, a malignant hematologist at Tampa General Hospital Cancer Institute.
- Additional tests may include kidney and liver function tests, lactate dehydrogenase (LDH) levels, molecular testing, and, in some cases, CT or PET scans. Bone marrow biopsies are often not needed at the time of diagnosis.
- After diagnosis, CLL is staged using the Rai system, but treatment decisions are based on more than stage alone. Many people can be safely monitored with a watch-and-wait approach, but it’s important to report any new or worsening symptoms to your healthcare team promptly, as they may signal it’s time to start treatment.
“The blood work is the most important thing that we really will look at for a CLL diagnosis,” Dr. Kerr explains. “We want a complete blood count with something called a differential. So we need to look at not just the total white blood cell count, but which of those cells are lymphocytes (a type of white blood cell). Those are the cells that the CLL came from.”
Read MoreWhen Does Lymphocytosis Become CLL?
However, not everyone with an elevated lymphocyte count has CLL. According to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), the diagnosis requires at least 5 × 10⁹/L monoclonal B lymphocytes in the blood that persist for at least three months. People with lower numbers of abnormal B cells are diagnosed with monoclonal B-cell lymphocytosis (MBL), a common precursor condition that affects about 10% of the general population and progresses to CLL at a rate of approximately 1–2% per year.Because many people are first identified after routine blood work reveals lymphocytosis, distinguishing MBL from CLL is an essential first step in the diagnostic evaluation.
While routine blood tests often provide the first clues, additional specialized tests help confirm the diagnosis and provide important information that guides treatment decisions.
Before moving on to those tests, doctors will also review your blood chemistries, including kidney and liver function, electrolytes, and an enzyme called lactate dehydrogenase (LDH). Rising LDH levels can sometimes indicate increased cell turnover and may suggest the disease is becoming more active, Dr. Kerr explains.
Flow Cytometry: A Key Diagnostic Test for CLL
Once a persistent lymphocytosis meeting the diagnostic threshold is identified, doctors order a specialized blood test called flow cytometry. This test confirms that the excess lymphocytes are monoclonal B cells and identifies the characteristic protein markers seen in CLL.
Dr. Kerr notes that white blood cells “have markers on the surface” and “function kind of like name badges so you can tell what type of cell that is. So we can see, hey, 50% of your white blood cells are CLL cells floating around the blood.”
For people with CLL, flow cytometry can:
- Confirm the diagnosis by detecting the characteristic pattern of proteins found on CLL cells.
- Measure the number of leukemia cells circulating in the blood.
- Distinguish CLL from other blood cancers, such as lymphoma or other forms of leukemia, which have different marker patterns.
- Guide treatment planning by providing information about the type and extent of the disease.
Additional Tests Used During a CLL Workup
Imaging, if needed, may be ordered, “which will be usually a CT scan or a PET scan,” he adds, but imaging is not generally needed for a diagnosis and is typically used to scan any concerning areas in the body that may be causing symptoms.
“And we often consider bone marrow biopsies. However, for this particular diagnosis, sometimes we can get enough information from the blood and we might forego a bone marrow biopsy at least upfront.”
Molecular Testing Helps Guide Treatment
Another important part of the evaluation—either at diagnosis or before starting treatment—is molecular and prognostic testing. These tests include FISH (fluorescence in situ hybridization), IGHV mutation status, karyotype analysis, and testing for certain genetic mutations. Together, they help doctors understand how the disease is likely to behave, predict whether it may respond to certain treatments, and choose the most appropriate therapy if treatment becomes necessary.
These tests help determine treatment selection, predict resistance to certain therapies, and are a vital part of the evaluation at diagnosis and before treatment begins.
Not Everyone Needs Treatment Right Away
One major thing to keep in mind when facing a CLL diagnosis is that doctors sometimes use a watch-and-wait approach before exploring treatment options, especially if the patient is asymptomatic.
During watchful waiting, your doctor will monitor you with regular blood tests and exams. Treatment usually begins only if the disease starts to progress or causes symptoms, so it’s important to let your healthcare team know about any new or worsening symptoms between scheduled visits. Signs to watch for include:
- Severe or persistent fatigue
- Drenching night sweats
- Unexplained fever without an infection
- Unintentional weight loss
- Enlarging lymph nodes or spleen that cause discomfort
- Worsening anemia or low platelet counts shown on blood tests
- A rapid increase in the number of leukemia cells
“When you hear the word cancer, it makes everyone nervous. It’s a scary word to hear,” Dr. Kerr says. “The important thing about CLL is that having the diagnosis does not mean you have to be on treatment.”
Staging CLL
CLL is classified using something called the Rai staging system (some clinicians use the Binet staging system, but Rai is more common in the United States). Determining the stage helps doctors figure out the best course of treatment, or if treatment is even necessary at the time of diagnosis.
When staging CLL, “if you simply have the abnormal white blood cells, but you do not have any abnormal lymph nodes or an enlarged spleen and your other blood counts look good, that would be what we call a ‘Rai stage zero,'” Dr. Kerr says.
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“However, if you have enlarged lymph nodes, enlarged spleen, and you start to see those normal cells go down, that might be a more advanced, or a Rai stage three or four.”
Dr. Kerr notes that Rai staging “isn’t always criteria for treatment. That’s just how we stage the initial disease. Someone with a Rai stage two disease doesn’t necessarily have to have treatment.”
Stage zero patients are not always in the clear, however. “I have certainly started treatment for patients who had Rai stage zero disease based on their symptoms,” he adds.
Rai Staging System
The Rai system divides CLL into 5 stages based on the results of blood tests and a physical exam:
Stage 0: No enlargement of the lymph nodes, spleen, or liver, with red blood cell and platelet counts near normal.
Stage I: Lymphocytosis with enlarged lymph nodes, though the liver and spleen are not enlarged, with red blood cell and platelet counts near normal.
Stage II: Lymphocytosis with liver and/or spleen enlarged; lymph nodes may or may not be enlarged, and red blood cell and platelet counts are still near normal.
Stage III: Lymph nodes, liver, or spleen may or may not be enlarged; red blood cell counts are low, which is considered anemia, yet platelet counts are still near normal.
Stage IV: Lymphocytosis with enlarged lymph nodes, spleen, or liver; there may be too few red blood cells, and platelet counts are low, which is known as thrombocytopenia.
Once your doctor goes over the results of your blood work and any other tests performed, they will assess your stage, and — depending on whether or not you are presenting any symptoms — will carefully determine the best plan for you moving forward.
Questions To Ask Your Doctor
- What stage is my CLL and what does that mean for treatment?
- Do I need treatment right away, or is a watch-and-wait approach better?
- Why is watchful waiting considered safe in my case?
- How often will I need blood tests, scans, or follow-up appointments?
- What signs or symptoms would mean it’s time to start treatment?
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