Chronic Lymphocytic Leukemia
Frequently Asked Questions
General Information
Frequently Asked Questions
What is chronic lymphocytic leukemia (CLL)?
Can CLL be cured?
Are there other types of leukemia?
Are there subcategories of CLL?
How common is CLL?
What causes CLL?
Is CLL hereditary?
What are the stages of CLL?
What are constitutional symptoms?
What is the survival outlook for people with CLL?
What is "smoldering" CLL?
 
What is chronic lymphocytic leukemia (CLL)?
Chronic lymphocytic leukemia (CLL) is a form of blood cancer in which too many lymphocytes are found in the body. These abnormal lymphocytes accumulate in the bone marrow, blood, lymph tissue, and other organs of the body and are unable to perform their proper functions. Lymphocytes are a specific type of white blood cell. The two main types of lymphocytes are B-cells and T-cells. Approximately 95% of CLL cases involve B-lymphocytes; the remainder are T-cell leukemias. The CLL FAQ deals primarily with B-cell CLL.

Historically, CLL was thought to be a disease characterized by the accumulation of malignant B-lymphocytes due to abnormally extended life spans. Unlike other cancers, CLL was considered a disease of cell accumulation rather than cell proliferation. However, recent data suggests that both increased lymphocyte birth rates and decreased lymphocyte death rates are factors in the relentless accumulation of malignant B-lymphocytes that occurs in CLL. The progressive accumulation of these malignant lymphocytes eventually causes diminished production of normal bone marrow and blood cells.

Some patients have no symptoms at all when diagnosed with CLL and are said to be asymptomatic. This can continue for many years. Others may experience more rapid onset of symptoms and a more aggressive form of the disease. Symptoms may include fatigue and enlarged lymph nodes, spleen, and liver. Severe anemia as well as low platelet counts, which can put patients at risk of bleeding, may also occur. Patients with CLL may also develop serious infections because of reduced numbers of infection-fighting cells known as neutrophils. (see also: What is Monoclonal B-cell lymphocytosis (MBL)? and What is small lymphocytic lymphoma (SLL)?)

Can CLL be cured?
CLL is considered an incurable disorder; however, treatment can often control the disease and its symptoms.

Many people with CLL continue to have a relatively normal and active lifestyle for many years—in some cases for decades. In this way, CLL is quite unlike acute leukemias, which are far more devastating. Many new treatments for CLL are currently under investigation, and there is good reason for newly diagnosed patients to feel hopeful that long term remissions are reasonably possible. Perhaps a cure is also just around the corner. Bone marrow transplantation currently offers promise as a potential cure, in that several CLL patients who have had bone marrow transplants have had no recurrence of disease. However, this procedure is usually reserved for a subset of patients with progressive disease and who have exhausted other treatment options.

Patients are encouraged not to panic and not to think of CLL as a “death sentence”.

Are there other types of leukemia?
There are several types of leukemia, which differ dramatically in prognosis, treatment, and symptoms. Leukemia is either acute or chronic and usually arises in either of the two main types of white blood cells—lymphoid cells or myeloid cells. When leukemia affects the lymphoid cells, it is called lymphocytic leukemia. When myeloid cells are affected, the disease is called myeloid or myelogenous leukemia. The most common types of leukemia are:

Acute lymphocytic leukemia (ALL) – ALL is the most common type of leukemia in young children. This disease also affects adults, especially those ages 65 and older. ALL can be divided into subcategories by the type of cell or the genetic damage found in the cells.

Acute myeloid leukemia (AML) – AML occurs in both adults and children. This type of leukemia is sometimes called acute nonlymphocytic leukemia (ANLL). AML can be subdivided into categories based on the genetic damage found in the cells.

Chronic lymphocytic leukemia (CLL) – CLL most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children.

Chronic myeloid leukemia (CML) – CML occurs mainly in adults. A very small number of children also develop this disease.

These are not the only types of leukemia, but they are the most common forms of the disease.

Are there subcategories of CLL?
While CLL has not been formally classified into subcategories, the division of B-CLL into stable and progressive disease was noted in the 1960’s, and it is now generally agreed that there are two subsets of CLL based on IgVH gene mutational status. (see also: What is the significance of IgVH gene mutational status in CLL?)

As we learn more about CLL and as more sophisticated techniques become available for studying CLL at a molecular level, formal subcategories may be identified. This, in turn, may help to explain why CLL progresses very differently among patients and why response to treatment can vary widely. Some differences in disease progression and response to treatment are no doubt attributable to patient differences such as age and general health, but we may find that additional differences in CLL also exist.

How common is CLL?
CLL is the most common form of leukemia in the western world. It accounts for approximately 25 to 30 percent of all leukemias. It occurs more frequently in older individuals but is seen increasingly in younger patients as well. The median age at diagnosis is 72 years.

Approximately 4.2 new cases per 100,000 Americans are diagnosed each year. CLL is almost twice as common in men as in women. In men approximately 5.7 new cases per 100,000 are diagnosed, and in women 3.0 new cases per 100,000 are diagnosed.

What causes CLL?
The cause or causes of CLL are not known. Scientists know that CLL occurs in males more often than females and in white people more often than in black people. However, they cannot explain why one person gets CLL and another does not.
Is CLL hereditary?
Clusters of CLL in families have been reported, and first-degree relatives of patients with CLL have a threefold-increased risk for CLL compared with the general population.
What are the stages of CLL?
Staging for CLL is used primarily for treatment planning. Two frequently used staging systems are the Rai system and the Binet system. The Rai staging system was introduced in the mid 1970’s, and a modified version was introduced in 1987. Both the original Rai staging system and the modified version are still in use. The Rai staging system is used primarily in North America while the Binet staging system is commonly used in other parts of the world.

In any stage, treatment planning is different for disease that has not responded to treatment (refractory disease) than for newly diagnosed and untreated disease. Details of the Rai and Binet staging systems are:

Rai Staging System

Stage 0 – There are too many lymphocytes in the blood, but there are usually no other symptoms of leukemia. Lymph nodes and the spleen and liver are not swollen, and the number of red blood cells and platelets is normal.

Stage I – There are too many lymphocytes in the blood and lymph nodes are swollen (lymphadenopathy). The spleen and liver are not swollen and the number of red blood cells and platelets is normal.

Stage II – There are too many lymphocytes in the blood, lymph nodes are swollen, and either the liver is swollen (hepatomegaly) or the spleen is swollen (splenomegaly).

Stage III – There are too many lymphocytes in the blood and too few red blood cells (anemia). Lymph nodes and the liver or spleen may be swollen.

Stage IV – There are too many lymphocytes in the blood and too few platelets (thrombocytopenia). The lymph nodes, liver, or spleen may be swollen, and there may be too few red blood cells (anemia).

Modified Rai Staging System

Low-risk group – Rai Stage 0 (lymphocytosis only – blood and marrow).

Intermediate-risk group – Rai Stage I (lymphocytosis and enlarged nodes) and Stage II (enlarged spleen and/or liver) combined.

High-risk group – Rai Stage III (lymphocytosis with anemia, defined as hemoglobin of less than 11 gm%) and Stage IV (platelets of less than 100,000 per microliter of blood) combined.

Binet Staging System

Clinical stage A – Red blood cells and platelets are in the normal range and there are fewer than three areas of lymphoid involvement.

Clinical stage B – Red blood cells and platelets are in the normal range and there are three or more areas of lymphoid involvement.

Clinical stage C – Below normal numbers of red blood cells (anemia) and/or platelets (thrombocytopenia) regardless of the number of areas of lymphoid involvement.

Some consideration has been given to an integrated system utilizing both the Rai and Binet staging systems. According to the integrated system, each Binet stage is further identified by the appropriate Rai stage (e.g., A-0, A-I, AII, B-I, B-II, C-III, C-IV). The integrated system has not been widely accepted, and most physicians continue to use either the Rai or Binet system. The Rai and Binet systems are not the only staging systems for CLL, but they are the most widely used systems.

What are constitutional symptoms?
Constitutional symptoms are those that relate to the system as whole; not local. The following are constitutional symptoms in CLL:
  • Significant fatigue – performance status 2 or worse (see: What is performance status?)
  • Unintentional weight loss – loss of 10% or more with the previous six months
  • Fevers – higher than 38° C for two or more weeks without any other evidence of infection
  • Night sweats – for more than one month without evidence of infection
What is the survival outlook for people with CLL?
The National Cancer Institute-Sponsored Working Group (NCI-WG) recommends usage of the “3-risk group” modification of the original five-stage Rai staging system. The “3-risk group” modification is as follows:
  • Low-risk group – Rai Stage 0 (lymphocytosis only – blood and marrow).
  • Intermediate-risk group – Rai Stage I (lymphocytosis and enlarged nodes) and Stage II (enlarged spleen and/or liver) combined.
  • High-risk group – Rai Stage III (lymphocytosis with anemia, defined as hemoglobin of less than 11 gm%) and Stage IV (platelets of less than 100,000 per microliter of blood) combined.

The median life expectancy of patients in the low-risk group is 14+ years, the intermediate-risk group 8 years, and the high-risk group about 4 years. For additional perspective on medians, there is an excellent article entitled, The Median Isn’t the Message, which is available at http://www.cancerguide.org/median_not_msg.html.

What is “smoldering” CLL?
In early-stage disease (Rai Stage 0 to II), a group of patients with “smoldering” CLL has been identified. These patients have hemoglobin of more than 13 grams per deciliter of blood (13g/dL), platelet count of greater than 150,000 per microliter, and lymphocyte count of less than 30,000 per microliter. They also have a doubling time of peripheral lymphocytes of longer than 1 year and non-diffuse bone marrow histology. These patients have a survival equivalent to an age- and sex-matched population.