Chronic Lymphocytic Leukemia
Frequently Asked Questions
Related Disorders
Frequently Asked Questions
What is monoclonal B-cell lymphocytosis (MBL)?
Does CLL lead to other forms of cancer?
What is the difference between CLL and lymphoma?
What is small lymphocytic lymphoma (SLL)?
What is hairy cell leukemia (HCL)?
What is prolymphocytic leukemia (PLL)?
What is Richter's syndrome?
What is mantle cell lymphoma (MCL), and is it related to CLL?
Is there a connection between shingles and CLL?
What is autoimmune hemolytic anemia (AIHA)?
What is idiopathic thrombocytopenic purpura (ITP)?
What causes night sweats in CLL?
What is monoclonal B-cell lymphocytosis (MBL)?
Monoclonal B-cell lymphocytosis is a condition in which an individual has all the characteristics of CLL in a blood test but has a lymphocyte count of less than 5,000 (5000 lymphocytes per microliter of blood). This condition is known as MBL.

Such low levels of CLL cells are detected in approximately 3% of the general population. Chromosomal abnormalities are frequently detected in this group of apparently normal patients. It is estimated that 1-2% of patients per year with MBL will progress to CLL and require treatment.

Does CLL lead to other forms of cancer?
There is an increased risk of second and even third malignancies, which are attributed to failure of immune surveillance. Treatment-induced acute leukemias may also occur in a small percentage of patients. Transformation of CLL to diffuse large cell lymphoma (Richter’s syndrome) is also a possibility.
What is the difference between CLL and lymphoma?
CLL and the other leukemias are primary disorders of the bone marrow, whereas, the lymphomas are malignant disorders that arise in the lymphoid tissue, most often showing up as solid tumors in nodes found throughout the body.

There are two broad groups of lymphomas: the non-Hodgkin’s lymphomas (NHL) and Hodgkin’s disease (Hodgkin’s lymphoma). Like the leukemias, non-Hodgkin’s and Hodgkin’s lymphomas are categorized into several sub-types. Classification of the lymphomas is a controversial area that is undergoing evolution. Following is a modified version of the Revised European American Lymphoma (REAL) Classification:
Indolent Non-Hodgkin’s Lymphomas

  • Follicle center cell lymphoma, follicular
    • Grade I follicular small cleaved cell
    • Grade II follicular mixed
    • Diffuse small cleaved cell
  • Diffuse small lymphocytic lymphoma
  • Marginal zone lymphoma
    • MALT (extranodal)
    • Monocytoid B-cell lymphoma (nodal)
    • Splenic lymphoma with villous lymphocytes
  • Mycosis fungoides/Sezary syndrome
Aggressive Non-Hodgkin’s Lymphomas
  • Diffuse large cell lymphoma (includes diffuse mixed cell, diffuse large cell, immunoblastic)
  • Burkitt’s lymphoma/diffuse small non cleaved cell lymphoma
  • Lymphoblastic lymphoma
  • CNS lymphoma
  • Adult T-cell lymphoma
  • Mantle cell lymphoma
  • Post-transplantation lymphoproliferative disorder
  • AIDS-related lymphoma
  • True histiocytic lymphoma
  • Primary effusion lymphoma
Hodgkin’s Disease
  • Lymphocyte predominance
  • Nodular sclerosis
  • Mixed cellularity
  • Lymphocyte depletion
What is small lymphocytic lymphoma (SLL)?
Small lymphocytic lymphoma (SLL) is one of the subtypes of non-Hodgkin's lymphoma. Unlike the other lymphomas, SLL overlaps with CLL both clinically and morphologically.

Some practitioners consider SLL and CLL the same disease, differentiated only by how symptoms are presented in early stage disease. CLL shows up primarily in the bone marrow and peripheral blood, while SLL presents itself primarily in the lymph nodes or lymphoid tissues. Other practitioners see them as different diseases because of the different signs and symptoms that are associated with each. For example, a patient with SLL may complain of swollen nodes and of a low-grade fever while a patient with CLL might not have any complaints or a complaint of fatigue. A third group of practitioners visualizes these two diseases as the two ends of a straight line. They are connected and, as the disease progresses, come closer to each other, but they start out far apart.

What is hairy cell leukemia (HCL)?
Hairy Cell Leukemia is an uncommon form of chronic leukemia that, like CLL, affects B-lymphocytes. The median age at presentation of HCL is 55 years, and there is a 5 to 1 male predominance.

Most patients with HCL present with gradual onset of fatigue, others experience symptoms related to spleen enlargement, and yet others come to attention because of infections. Upon physical examination, an enlarged spleen (splenomegaly) is almost invariably present and may be massive. The liver is enlarged in approximately fifty percent of cases, but swollen lymph nodes are uncommon.

Laboratory findings include B-lymphocytes, which have characteristic "hair-like" projections when examined under the microscope and reduced numbers of all types of blood cells (pancytopenia). On immunophenotyping, the leukemic cells co-express the antigens Cd11c and CD22.

HCL is very responsive to treatment with cladribine (Leustatin, 2CdA) and pentostatin (Nipent, 2’-deoxycoformycin).

What is prolymphocytic leukemia (PLL)?
Prolymphocytic leukemia (PLL) is a rare variant of CLL. It is a related but distinct B-cell disorder and is one of the B-cell malignancies most often confused with CLL. Most PLL patients are diagnosed initially with PLL; however, some will have initially been diagnosed with CLL, which subsequently transforms and takes on the appearance of PLL.

Unlike CLL, the abnormal lymphocytes seen in PLL are immature cells (prolymphocytes), which are not normally seen in the peripheral blood. The diagnosis is PLL rather than CLL if more than half the leukemic cells are prolymphocytes. If there are prolymphocytes present, but they make up less than half of the abnormal cells, the condition is called mixed CLL/PL. A patient with PLL will typically have a very large spleen and a very high white blood count. Most patients do not have enlarged lymph nodes, but may have non-specific symptoms like tiredness and weight loss. PLL tends to be more aggressive than CLL and is less responsive to therapy. Approximately 10 percent of patients who have chronic lymphocytic leukemia will have their illness transform and take on the appearance of prolymphocytic leukemia. The condition T-cell PLL has no relationship to CLL or B-PLL.

What is Richter's syndrome?
Richter's syndrome is the transformation of CLL to diffuse large cell lymphoma, which is one of the non-Hodgkin's lymphomas. Laboratory tests usually confirm that the lymphoma originates from the same population of cells as the leukemia. In this case, it is considered a transformation. If the lymphoma arises from different cells, it can be regarded as a secondary cancer arising by chance.

Richter's syndrome is suspected in any CLL patient who shows the onset of otherwise unexplained fever, weight loss, increase in serum lactate dehydrogenase (LDH), localized enlargement of lymph nodes, and enlargement of the liver and spleen. In this situation, biopsy of the newly enlarged lymph nodes is indicated to determine whether or not lymphoma cells are present.

There are no obvious causes for the transformation of CLL to Richter's syndrome, which can affect patients at any stage of CLL, including those in complete remission. The incidence of Richter’s transformation, which carries a poorer prognosis than CLL, has been reported at between three and ten percent.

What is mantle cell lymphoma (MCL), and is it related to CLL?
Mantle Cell Lymphoma (MCL) frequently comes up in the discussion of CLL because its clinical presentation is extremely similar to that of CLL. Enlarged liver and spleen (hepatosplenomegaly) and elevated lymphocyte counts (lymphocytosis) are common in both diseases. However, MCL is a non-Hodgkin's lymphoma, which has its origins in the lymph nodes, whereas CLL is a leukemia and has its origins in the bone marrow.

Flow cytometry results of MCL are very similar to those of CLL. CLL lymphocytes coexpress B-cell antigens CD19 and CD20 along with the T-cell antigen CD5. With the exception of SLL, MCL is the only disease that also expresses these antigens. However, CLL lymphocytes also express CD23; whereas, MCL lymphocytes do not. This lack of expression of CD23 is useful in distinguishing MCL from CLL. In addition, the antigen density of CD20 is typically much lower in CLL than it is in MCL. This is one of the reasons why rituxan, the anti-CD20 monoclonal antibody, is more effective in the treatment of lymphoma than it is in CLL. For more information on CD markers and flow cytometry see, What is flow cytometry?

MCL is also known as small-cleaved lymphoma, intermediate differentiation lymphoma, centrocytic lymphoma, and mantle zone lymphoma, but it should not be confused with marginal zone lymphoma. MCL comprises approximately 5 percent of all non-Hodgkin's lymphomas. The median age at diagnosis is approximately 55 years and approximately 80 percent of patients are males. Three subtypes of MCL have been noted: Nodular MCL, Diffuse MCL and Blastic MCL. MCL, like CLL, is currently considered incurable.

Is there a connection between shingles and CLL?
Shingles is an infection caused by the varicella-zoster virus, which is the same herpes virus that causes chickenpox. Shingles occurs in people who have had chickenpox and is a reactivation of the dormant varicella-zoster virus. The disease generally affects the elderly, although it occasionally occurs in younger and/or immunodeficient individuals. CLL patients fall into the latter category, and for this reason, they are more prone to reactivation of the varicella-zoster virus. It is not possible to catch shingles from somebody who has it. A person can only get shingles by having chicken pox earlier in life. However, an adult with shingles can cause a person who has not had chicken pox to get chicken pox.

The first sign of shingles is usually a tingling feeling, itchiness, or stabbing pain on the skin. This progresses to a rash that appears as a band or patch of raised dots on the side of the trunk or on the face. The rash develops into small, fluid-filled blisters, which begin to dry out and crust over within several days. Shingles can be very painful and itchy but is not generally dangerous to healthy individuals. However, people with shingles on the upper half of the face should seek medical attention immediately as the virus may cause serious damage to the eyes. The rash and pain associated with shingles usually disappear within 3 to 5 weeks, although, the pain can persist much longer and be quite intense. The pain that continues after the rash from shingles has healed is called, postherpetic neuralgia (PHN).

Most people who have shingles have only one occurrence of the disease in their lifetimes; however, individuals with impaired immune systems may suffer repeated episodes. Treatment for shingles includes antiviral drugs such as acyclovir (Zovirax). The severity and duration of an attack can be significantly reduced by immediate treatment.

A shingles vaccine was introduced a few years ago, but this live vaccine is not recommended for people with CLL. (See also: What should I know about vaccinations?)

What is autoimmune hemolytic anemia (AIHA)?
Autoimmune hemolytic anemia (AIHA) is a form of anemia that is commonly associated with CLL. It is estimated that 10% to 20% of CLL patients may develop AIHA sometime during the course of their illness. The development of this condition does not have implications for the staging of CLL; rather, it is usually reported as a complication of progressing disease.

In AIHA, the immune system malfunctions and develops antibodies against the patient's own red blood cells and destroys them prematurely. Symptoms of AIHA include nosebleeds, bleeding gums, chills, fatigue, pallor, shortness of breath, rapid heart rate, jaundice, and swelling of the spleen (splenomegaly). Diagnosis is confirmed with a test called the direct antiglobulin test or Coombs test. The mainstay treatment of AIHA associated with CLL is prednisone. Some forms of AIHA are treated by splenectomy because the spleen destroys antibody-coated, red blood cells. Removing the spleen allows the antibody-coated cells to function longer.

AIHA is not the only form of anemia that occurs in CLL patients. Anemia can also occur as a result of chemotherapy, due to blood loss, and in advanced CLL when malignant lymphocytes compromise the production of normal blood cells. Other forms of anemia can also occur, but these are the most common reasons for anemia in CLL patients.

What is idiopathic thrombocytopenic purpura (ITP)?
Idiopathic Thrombocytopenic Purpura or Immune Thrombocytopenic Purpura is an autoimmune disease. These are a class of diseases where the body considers a normal part of itself foreign (in this case platelets), and it attacks the "foreign cells". In ITP, the platelets are "coated" by antibodies and the spleen recognizes this as something to be removed from circulation. As a result, these platelets are trapped in the spleen until they die and are recycled. The problem is that the body keeps making the antibody so a replacement generation of platelets also gets coated, and the cycle continues.

Thrombocytopenia means low platelets, and purpura refers to the purple looking bruises and spots that appear under the skin and mucous membranes (petechiae and ecchymoses). So, ITP is a bruising that is caused by low platelets, which are the result of an immune dysfunction.

Some cases of ITP are caused by drugs and others are associated with infection, pregnancy, or immune disorders. About half of all cases are classified as "idiopathic" meaning the cause is unknown. Approximately 2 – 4% of CLL patients develop ITP. It can occur at any stage of CLL.

The main symptom of ITP is bleeding which can include bruising and tiny red dots on the skin or mucous membranes. In some instances bleeding from the nose, gums, digestive or urinary tracts may also occur. ITP is often accompanied by fatigue and sometimes by depression.

ITP is characterized more by its description than the specific properties of the disease. It is the diagnosis when platelets are abnormally low and other diseases that can cause low platelets have been ruled out. The diagnosis of ITP is supported when a complete blood count and bone marrow biopsy or aspirate finds normal or increased platelet forming cells (megakaryocytes).

Treatment is based on symptoms. In some cases no treatment is needed. In most cases, corticosteroids, such as prednisone, are the first line of treatment because corticosteroids prevent antibody formation. Intravenous infusions of immunoglobulin (IVIg) may be used as the next line of treatment. Splenectomy is successful in about 75% of patients who have not responded to other therapy. While it may seem overly aggressive to remove the spleen, many people think that it is the spleen that is actually causing the problem through overzealous removal of the platelets. These platelets can and do work just as well as uncoated platelets, so removing the spleen allows them to live a "normal" lifespan and work as they should. Other drugs used with refractory ITP include cyclosporine, vincristine, danazol, and azathioprine (imuran).

What causes night sweats in CLL?
As CLL progresses, some patients will experience night sweats. It is important to advise your hematologist/oncologist if this occurs, as this is an indication that your CLL is progressing.

There are no clear-cut answers about why night sweats occur in CLL. There are some plausible explanations about metabolic dysfunction and changes in certain hormone levels (somewhat similar to the night sweats experienced by peri-menopausal women), but there are no clear-cut answers.

CLL-related night sweats are usually all over the body and often necessitate a change of bedding and nightclothes, whereas, menopausal night sweats tend to be less severe and are usually confined to the chest, neck, and head areas, and sometimes the bend of the elbow or knee.