Joseph R. Anticaglia, MD
Medical Advisory Board
Chronic lymphocytic leukemia (CLL) is a type of blood cancer that grows slowly, more commonly in men and typically diagnosed after the age of 60 years. It is rarely seen in children. The cancer particularly damages B lymphocytes which are white blood cells. The lymphocytes develop from stem cells in the bone marrow. The cancer interferes with B lymphocyte production of antibodies that help your body fight infections.
This blood cancer is often diagnosed incidentally after a routine blood test demonstrates an elevated white blood cell count (lymphocytosis). Such was the situation with Mark, a 74 year old retired schoolteacher. He thought he was in excellent health. During his annual visit, his Family Doctor said:
“Hi Mark, good to see you. I noticed you have lost about ten pounds since our last visit. And the size of your waist has reduced in size by one and a half inches. All good news. Have you been trying to lose weight? How do you feel?”
“I feel fine except that I seem to get tired a bit more easily. I’ve been trying to lose a few pounds, but I haven’t been dieting except that I’ve cut down on sweets and snacks.”
After the physical examination, his doctor said, “Everything looks fine. I’ll order routine blood work, urinalysis and see you in a year. I’ll call you if anything is unusual. Regards to the family.”
Mark got the call from his doctor who said, “I reviewed you blood tests and you have too little red blood cells and too many white blood cells.”
“What does that mean?”
“You have a slight case of anemia which means you don’t have enough healthy red blood cells circulating in your body. This causes a decrease in the amount of oxygen in the bloodstream which is needed by your body to function optimally. This finding might explain why at times you feel tired.”
“Also, the report indicates you have lymphocytosis, meaning that you have an abnormally elevated number of white blood cells in the blood. Your bone marrow, the soft, spongy tissue in the central part of the bone, contain stem cells that make healthy red blood cells. They also make white blood cells that help make up the immune system which fights infections.”
“There are several reasons why there’s an increase in the number of WBCs. One important reason, and I know it comes as a shock, is to rule out cancer. I think it’s best to consult a specialist concerning this finding, and see what he says.”
“Where do we go from here?”
“I recommend you see my colleague, an oncologist a cancer doctor who has a particular interest in blood disorders. This is his name and phone number. I’ll send your records over to him with the recent lab tests. Don’t hesitate to call me if you have any questions.”
The oncologist ordered a barrage of tests, reviewed the findings with Mark and gobsmacked him with the staggering news that he had Chronic Lymphocytic Leukemia, (CLL)..
He said, “Here’s the good news! You have an early stage of this disease. You don’t need drugs or any other type of treatment at this stage of the cancer. I’ve managed hundreds of patients with your form of cancer without medications who have lived well for ten years and longer. I will actively monitor your condition.
“See you in four months for reevaluation and we’ll repeat the examination and the tests. At this time, as I said, no medications. Go about your normal routine, eat a healthy diet and do moderate exercise on a daily basis. Enjoy a good dinner tonight with a glass of good wine! Call me if you have any questions.”
Symptoms
In the early stages of CLL, patients usually have no symptoms. People may feel fatigued because CLL can cause anemia. Patients may have fever because of poorly functioning white blood cells. Cancer patients experience unintended weight loss because of the release of cytokines into the blood. Cytokines help fight disease, but it can also causes weight loss. Patients may also complain of abdominal fulness due to enlargement of the spleen. Night sweats is another symptom of chronic lymphocytic leukemia. The body may raise its temperature to fight infection or to fight cancer cells. Swollen lymph nodes, and an enlarged liver and spleen are other findings that may be diagnosed with this disease (hepatosplenomegaly).
Two Kinds of CLL Cells
Chronic lymphocytic leukemia attacks two types of white blood cells, B cells and T cells. The cells undergo a malignant transformation becoming leukemia cells. These cancer cells grow and multiply crowding out normal B and T cells. The more they grow, the more we’re subjected to infections and other problems.
- B-cells’ lymphocytes make antibodies that target foreign invaders viruses, bacteria, including cancer cells in the extracellular fluid — outside the cell. The vast majority of people with chronic lymphocytic leukemia have an overgrowth of abnormal B-cells in the bloodstream, lymph nodes, spleen and liver.
- B cells and T cells are white blood cells that form a one-two punch in protecting us from foreign substances. T cells are part of the immune system that seek, attack and destroy foreign invaders which reside and hide themselves inside the cell. Abnormal T cell lymphocytes weaken our body’s ability to defend itself against foreign intruders.
What Are the Risk Factors for CLL?
Medical scientists don’t know what causes a person’s chromosomes and genes to change into the cancerous blood cells of CLL. And most patients with CLL have few if any known risk factors. Risk factors include a family history of the disease, men over the age of 60 years, and exposure to certain chemicals, for instance Agent Orange.
Diagnosis
The hallmark of CLL is an isolated lymphocytosis, that is, a white blood count that is usually greater than 20,000 per microliter. Other, more advanced laboratory studies are used to diagnose this condition. Bone marrow biopsies are used much less frequently — see glossary.
Staging Systems for Chronic Lymphocytic Leukemia
Staging systems for CLL have proved to be useful guides for clinicians to manage this cancer. One approach is to stage this condition into three categories.
Low Risk — Rai stage 0
People have lymphocytosis and abnormal white blood cells in their blood and/or bone marrow.
Intermediate Risk — Rai stage 1 or stage 2
People have lymphocytosis, enlarged lymph nodes and an enlarged spleen and/or liver.
High Risk — Rai stage 3 or stage 4
People have anemia or thrombocytopenia.
Treatment Options for CLL
Treatment varies based on symptoms, physical findings, test results, and the stage of the disease.
- Active monitoring:
Clinicians watch and wait for symptoms and signs to treat. - Targeted therapy:
This therapy focuses on neutralizing CLL cancer cells either by preventing their growth or killing the cancerous white blood cells. - Chemotherapy:
Chemotherapy works by damaging cancer cells as they divide. - Immunotherapy:
This treatment boosts your body’s immune system so it can slow the growth or destroy the cancerous cells - Radiation Therapy:
This treatment is used to mitigate CLL symptoms.
Complications
Because people suffering from chronic lymphocytic leukemia do not have adequate, healthy white blood cells, they may experience frequent infections, be prone to certain cancers such as skin cancers, change into a more aggressive form of cancer, or develop autoimmune diseases. In addition, one needs to be aware of the potential side effects of different cancer treatments
As mentioned, CLL is a slow growing blood cancer. It develops almost exclusively in your B cells, rarely seen in children and most often diagnosed incidentally, as in Mark’s case, in men after the age of 60 years. Low risk patients do not required treatment for many years, and have led productive lives without treatment.
Although there is no cure for chronic lymphocytic leukemia at present, when treatment is indicated, researchers have developed drugs and immunotherapies which put CLL into remission (periods of time without symptoms) and by so doing help patients experience a prolonged, good quality of life.
Glossary
Diagnosis The essential findings in chronic lymphocytic leukemia is lymphocytosis with white blood cells greater than 20,000 per microliter and coexpression of CD19,and CD5 on the lymphocytes. Your doctor will take your medical history, perform a physical examination, and order tests such as flowcytometry, genetic tests in addition to a CBC, complete blood count to diagnose this blood cancer.
Richter’s syndrome is a rare transformation of chronic lymphocytic leukemia into an aggressive form of cancer, most commonly, diffuse large cell lymphoma.
Staging Systems
Rai Staging System categorizes the cancer by the likelihood that the cancer will get worse and require treatment. It correlates with the low, intermediate and high risk staging of CLL — see above.
Binet staging system uses letters to classify CLL by how much the cancer has spread throughout the body.
Stage A
You have fewer than three groups of enlarged lymph nodes.
Stage B
You have three or more groups of enlarged lymph nodes in your body, liver or spleen without a low level of red blood cells or low a low level of platelets.
Stage C
You have anemia, i. e., a low number of red blood cells, or thrombocytopenia, that is, a low number of platelets.
The American Cancer Society estimates about 20,700 new cases of chronic lymphocytic leukemia for the year 2024.
References
- Julie Marks; CLL in Later Stages; WebMD, Dec. 14, 2021
- American Cancer Society; How Is Chronic Lymphocytic Leukemia Diagnosed?;
- Canadian Medical Society; Disease progression of chronic lymphocytic leukemia
- Mayo clinic; High white blood Count; Dec. 15, 2022
- NHS; Chronic lymphocytic leukaemia; November 13, 2023
- American Cancer Society; What questions to ask about Chronic Lymphocytic Leukemia
- Leukemia and Lymphoma Society; Chronic Lymphocytic Leukemia
- Leukemia and Lymphoma Society; Disease progression of chronic lymphocytic leukemia
- Sameer A, Parlkin et al; How We Treat Richter Syndrome; Blood, March 13, 2013
- Joseph R. Anticaglia, MD; Amazing B Cells and Immunotherapy; Doctor’s Column HC Smart, 2024
- Joseph R. Anticaglia, MD; The Remarkable T Cells and the Immune System; Doctor’s Column HC Smart, 2024
This article is intended solely as a learning experience. Please consult your physician for diagnostic and treatment options.