Introduction

Chronic lymphocytic leukemia is a blood cancer in which the bone marrow produces too many lymphocytes (a type of white blood cell).  It is slow growing and often affects adults that are middle age and older and is one of the most common types of leukemia in adults. With improvements in oral chemotherapies and support medications, the success rate of treatment plans has increased in previous years. That being said, this type of cancer has been known to become a chronic illness.  Patients diagnosed with this type of cancer may have to manage the disease for decades instead of years.

Signs and Symptoms

Often times patients will be asymptomatic when diagnosed.  Sometimes vague symptoms such as feeling tired or weakness will bring them to their doctor for a check up. Early symptoms may include one or more of the following:

• Tired feeling

• Weakness
• Unexplained weight loss
• Persistent low-grade fever
• Night sweats
• Enlarged lymph nodes
• Fullness in their belly

These symptoms are directly related to the patient’s blood counts. When the doctor gets the results of a blood work, the test will often show a high number of lymphocytes. When the bone marrow becomes crowded due to excess lymphocytes, the leukemia cells replacing them cause a decrease in mature, properly functioning cells which leads to anemia, neutropenia, and thrombocytopenia.

1. Anemia – a shortage of red blood cells.  Due to the lower hemoglobin levels and less oxygen being transported to the cells, the patient may feel tired, weak, and short of breath.
2. Neutropenia – refers to a shortage of neutrophils which are necessary for fighting bacterial infections.
3. Thrombocytopenia – a shortage of platelets in the blood.  Platelets help to clot the blood. Patients with low platelets bruise easily, experience nose bleeds and bleeding gums.

Diagnosis

If CLL is suspected, there are a number of important exams for diagnosis:

• Patient health history
• Physical exam
• Complete blood count
• Flow cytometry
• Bone marrow study

The health care provider will take a complete health history asking for details on sleep patterns, energy level, appetite and lumps felt. If the history indicates the possibility of CLL, the provider will perform a physical exam paying close attention to areas with lymph nodes, and a complete blood count (CBC) and flow cytrometry will be run by the lab. If required, a bone marrow study will be collected by either the physician or an interventional radiologist.

Bone Marrow Study

Bone marrow studies are usually done just prior to treatment to determine how advanced the disease is.  It also serves as a bench mark for the oncologist to measure efficacy of treatment.

Bone marrow is usually aspirated from the patient’s pelvic bone. The pelvic bone is a very strong and dense bone and a fair amount of force and pressure is put on the bone when collecting the core sample. The patient must be able to lie on their stomach or side for the test, if these positions are physically impossible for the patient another sample site may be chosen.

The aspiration and biopsy are done at the same time to reduce risk of infection or bleeding with a second procedure. There is pain with the procedure as well; often this procedure is done in the oncologists office without analgesics. A local anesthetic is injected at the site but most physicians feel the procedure is done before the pain medications take effect, therefore they choose not to use them.

The aspirate collected is essentially liquid marrow. It is then put into test tubes for the lab. The biopsy, collected immediately after the aspirate, is a small piece of bone and marrow. These are carefully prepared at the bedside by the physician on eight different slides and test tubes. Additional tests that may be run with these samples include:

• Routine microscopic exams
• Cytogenetics
• Flourescent in situ hybridization (FISH)
• Molecular tests

Lymph Node Biopsy

A lymph node biopsy is where all or part of the lymph node is removed so that the tissue may be examined for presence of cancer cells.  This test is not always used.  Typically the physician will order this test when a lymph node is very swollen or has grown very large. It is the only way to verify it is not a second primary cancer site or a more aggressive form of lymphoma.  If a second primary cancer is found the treatment plan will change. If the lymphoma has become more aggressive the treatment plan may or may not change, but medication dose is usually increased.

Lumbar Puncture

Also referred to as a “spinal tap,” this is a procedure used to collect cerebral spinal fluid for examination and determining the presence of cancer cells in or around the brain and spinal cord.  Fortunately cerebral involvement is a rare occurrence with CLL, so this test should only be performed if this involvement is already suspected.

Imaging

There are several imaging tests that are used to determine the stage of the cancer, determine metastasis, and evaluate efficacy of treatment. The imaging tests use sound waves, magnetic fields and x-rays to produce a picture of the inside of the the body.  Imaging tests are never used to diagnose leukemia but rather to confirm location and size of the tumor.

Computerized Tomography Scan (CT scan)

CT imaging is a type of x-ray machine that takes images in multiple cross sections of an area of the body as it spins 360 degrees.  The computer then puts these cross sections together as a complete picture of the inside of the body.  This type of imaging is especially good for visualizing the internal organs.

Magnetic Resonance Imaging (MRI)

MRI scans also take detailed pictures of the soft tissue, but MRI uses radio waves instead of x-rays. The radio waves are absorbed and then released by the soft tissue.  A pattern is formed by this transfer of energy, and the pattern is then read by the computer and put into an image for the physician to interpret.  Different types of tissue, healthy and malignant, give off different patterns.  MRI is especially helpful in visualizing connective tissues.

Positron Emission Tomography (PET)

A PET scan is a procedure designed to find malignant cells in the body.  A small amount of radioactive glucose solution is injected into the patients vein.  The PET scan takes pictures and lights up brighter in the areas glucose is being used.  Malignant cells multiply rapidly using increased amounts of energy and consuming the glucose at higher rates.

Positron Emission Tomography with Computerized  Tomography (PET-CT)

PET-CT performs both tests at the same time giving a clearer image then either test can give on its own.

Stages of CLL

Like all cancers, CLL has been given a staging system to consistently determine the best treatment plan for the patient.  The following stages are used for chronic lymphocytic leukemia:

• Stage 0 – too many lymphocytes have been found in the blood but there are no other signs or symptoms of disease.  Stage 0 is indolent (slow growing).
• Stage I –  too many lymphocytes have been found in the blood and the lymph nodes are slightly enlarged.
• Stage II – too many lymphocytes have been found in the blood, the liver or spleen are enlarged and lymph nodes are larger than normal.
• Stage III – there are too many lymphocytes and too few red blood cells.
• Stage IV – there are too many lymphocytes and too few platelets in the blood. The lymph nodes are enlarged, the liver or spleen is enlarged. There may be too few red blood cells.

Adverse Prognostic Factors

There are other factors considered when predicting a patient’s prognosis and treatment options. The following is a list of factors that are linked with poor recovery and survival rates:

• Advanced age
• Male gender
• High levels of beta-2-microglobulin in the blood
• A doubling of a patient’s lymphocytic count in 6 months or less
• Diffuse pattern of bone marrow involvement
• Deletion of parts of chromosomes 17 and 11
• More than 20% of cells contain ZAP-70
• More than 30% of cells contain CD38
• High fraction of prolymphocytes in the blood.

Favorable Prognostic Factors

Just as there are adverse prognostic factors, there are favorable ones as well. This is a list that physicians agree predict a favorable response to treatment and high survival rate:

• Patient of younger age (less than 65 yrs)
• Female gender
• Deletion of parts of chromosome 13 (with no other chromosome abnormalities)
• CLL cells with a mutated gene for IGHV
• Low proportion of cells with ZAP-70
• Low proportion of cells with CD38

Treatment

Treatment is decided after taking many factors into account:

• stage of the patient’s cancer
• adverse and favorable prognostic factors
• overall health of the patient
• wishes verbalized by the patient

Types of Standard Treatment

There are five types of standard treatment used:

Observation

This is also called watchful waiting. The patient is closely monitored but no treatment is given.  If signs or symptoms appear or if there is change in the patient’s overall health more aggressive types of treatment may be pursued.

Radiation Therapy

The use of high-energy x-rays to kill cancer cells.  There are 2 types of radiation therapy:

• Internal radiation therapy uses radioactive substance that is contained in a delivery system, such as a needles, seeds, wires or catheters that are put directly into the cancer.
• External radiation therapy uses pinpoint radiation beams to eradicate the cancer cells.

Chemotherapy

These are drugs that stop the growth of the cancer either by killing them or interfering with their genetic programming preventing them from dividing.  Chemotherapy can be administered to the patient two ways, either orally or intravenously (IV).

If a patient is receiving IV chemotherapy, the drugs are given at a hospital or outpatient clinic on scheduled days for the length of a cycle. The schedule must be adhered to because the drug is given on specific days to interfere with the growth cycle of the cancer cells. Adhering to this schedule can be difficult for patients, as there may be many cycles in the treatment plan consisting of 2 or 3 days a week for as long as 18 months.  If the drug is not given at the exact times of cell division its efficacy decreases substantially.

Oral chemotherapy may be an option for some patients.  Oral drugs may be taken at home, some are daily for as long as the patient lives. Others work on the principal of interfering with the growth cycle of the cancer cell.  If the latter is the goal, the patient must still adhere to the strict schedule of medication administration but is able to do it from home.  In this case careful follow-up by nursing staff or their case manager is critically important in the patients success.

Surgery

Splenectomy – The spleen may be removed when the overpruduction of platelets is unmanageable.

Targeted Therapy (monoclonal antibodies)

Monoclonal antibodies are targeted treatment, meaning it can kill malignant cells without killing other nearby healthy cells. Monoclonal antibodies are given by infusion either alone or in conjunction with chemotherapy. They are made from a single type of an immune system cell and grown in a laboratory.

Summary

CLL is the most commonly diagnosed cancer in North America.  The chance of being diagnosed with CLL in a person’s lifetime is about 0.5%.  Thanks to clinical trials and the patients who participate, 83% of patients diagnosed with CLL will live more than 5 years.

The survival rate continues to improve as new chemotherapies, monoclonal antibodies and radiation techniques improve.

References:

Leukemia – Health Professional Version. Retrieved from https://www.cancer.gov/types/leukemia/hp.

Leukemia – Patient Version. Retrieved from https://www.cancer.gov/types/leukemia/. 

Randhawa, JK and Ferrajoli A. (2016). A review of supportive care and recommended preventive approaches for patients with chronic lymphocytic leukemia. Expert Rev Hematol., 9 (3), 235-244. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26652692.