Frequently Asked Questions
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.
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
- 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
- Lymphocyte predominance
- Nodular sclerosis
- Mixed cellularity
- Lymphocyte depletion
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.
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).
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.
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.
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.
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?)
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.
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).
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.