small lymphocytic lymphoma

Synonyms

2

Overview

Small lymphocytic lymphoma (SLL) is a B-cell lymphoma. Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are essentially the same disease, the only difference being where the cancer primarily occurs: When most of the cancer cells are located in the bloodstream and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved.

When the cancer cells are located in the lymph nodes, the disease is called SLL.

Chronic lymphocytic leukemia (CLL) is a cancer of the lymphocytes (a type of white blood cell) that begins in the stem cells of the bone marrow and then invades the blood. Overtime, CLL may also spread to the lymph nodes and other organs including the liver, spleen and lungs. It occurs when the stem cells that make lymphocytes become out of control and produce increasing amounts of abnormal lymphocytes (also called leukemic cells). Eventually, these abnormal cells replace normal lymphocytes and can crowd out other types of normal blood cells, leading to the features of the condition. The exact underlying cause of CLL/SLL is unknown; however, approximately 5% of affected people have other family members with the condition, which suggests there may be a genetic component in rare cases. The best treatment depends on many factors including the stage of the condition, the age of the affected person, the blood cell counts, whether the CLL has recurred, and the signs and symptoms present in each person. 

Symptoms

  • swelling of liver and/or spleen
  • enlargement of lymph nodes in the neck, underarm, stomach, or groin
  • fatigue
  • shortness of breath
  • anemia
  • brusing
  • night sweats
  • weight loss
  • frequent infections
  • often people infected with the disease present with no symptoms and enlarged lymph nodes are found during a routine exam
  • approximately 1/3 of disease patients live for years without any symptoms  

Causes

Chronic lymphocytic leukemia/small lymphocytic lymphoma starts with an abnormal mutation in the DNA of a lymphocyte. This change in the DNA—the chemical that gives instructions for cell development, reproduction, and breakdown—jumbles the directions for what is known as programmed cell death. Instead of maturing and eventually disintegrating into fragments that are digested by other cells, the abnormal lymphocytes persist for a period of weeks to months and accumulate in the body.

Scientists don't know exactly what causes a person to acquire the genetic mutations associated with CLL/SLL. In people, DNA is normally organized into 23 pairs of chromosomes that replicate themselves during cell reproduction. Some people with this disease are missing parts of their chromosomes; some may have an extra chromosome. The most common abnormality is a loss of part of chromosome 13; an extra copy of chromosome 12 is also common.

Diagnosis

After a diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma, the patient's lymphocytes should be evaluated for biological markers. Biological markers are the genetic characteristics of the leukemic cells that are used to predict how the cancer will progress. This information helps your doctor decide when to start treatment and which therapy to use. Patients with adverse biological factors are more likely to get worse and need treatment within a few years of diagnosis.

Biological markers fall into three main categories:

• Chromosomal abnormalities are the presence of additional segments or lack of segments in a cell's chromosome. There are many possible chromosomal abnormalities, the most common of which occur in chromosomes 13 and/or 17. Patients missing only a segment in chromosome 13 are considered at low risk for rapid progression of CLL/SLL, with a life expectancy usually exceeding 15 to 20 years when no other abnormalities are detected and they are in an early stage of the disease. A loss of a segment in chromosome 17 indicates a high risk of developing the most aggressive form of the disease, with an average life expectancy of less than five years.

• Immunoglobulin gene mutation status, known as IgVH, can be used to predict the outcome of patients with CLL/SLL. A mutated status is associated with the longest survival rates. This test is technically difficult to perform in the laboratory and generally only available at academic institutions with active research laboratories.

• Protein concentrations of substances known as ZAP-70 and CD38 can be used to predict the progression of CLL/SLL. A high concentration of either of these two markers has been linked to aggressive CLL/SLL. However, these markers may not be accurate in up to 30 to 40 percent of patients. In addition, some research shows that levels of CD38 may change over time. Although this test is available in most medical centers, the testing procedures used to analyze ZAP-70 and CD38 have not been standardised.

Prognosis

Because CLL/SLL is generally characterized by multiple disease relapses after responses to a variety of treatments, patients in remission should have regular visits with a physician who is familiar with their medical history as well as with the treatments they have received. Medical tests (such as blood tests and computed axial tomography [CAT] scans) may be required at various times during remission to evaluate the need for additional treatment.

Some treatments can cause long-term effects or late effects, which can vary based on duration and frequency of treatments, age, gender, and the overall health of each patient at the time of treatment. The doctor will check for these effects during follow-up care.

Survivors and their caregivers are encouraged to keep copies of all medical records and test results as well as information on the types, amounts, and duration of all treatments received. This documentation will be important for keeping track of any effects resulting from treatment or potential disease recurrences. 

Treatment

There are five general types of treatments for patients with CLL/SLL:
  • Watchful waiting (no treatment given) in which the patient is closely monitored to see if/when treatment should be started
  • Drug therapy, which includes one or more of the following types of drugs: 
  • Chemotherapy, which affects general cell growth and division
  • Monoclonal antibodies, which can specifically attack lymphoma cells
  • Targeted or biologic therapies, which affect special characteristics of tumor cells 
  • Stem cell transplantation
  • Radiation therapy, which uses high-energy radiation to kill lymphoma cells
  • Surgery to remove the spleen (splenectomy) 

Treatment is based on the severity of associated symptoms as well as the rate of cancer growth. If patients show no or very few symptoms, doctors may decide not to treat it right away, an approach referred to as "watch and wait" or "watchful waiting." Studies have shown that suitable patients who follow a "watch and wait" approach have outcomes similar to those being treated early in the course of their disease. However, patients with high-risk disease may need to start treatment right away.
There are many current first-line treatment options for CLL/SLL. The choice of treatment will depend on the stage of the disease, whether or not the patient is experiencing symptoms, the age and overall health of the patient, and the benefits versus side effects of treatment. It is not yet clear whether or not stem cell transplantation is helpful for patients with CLL/SLL. Stem cell transplants are usually done as part of a clinical trial in patients with high-risk or relapsed (disease returns after treatment)/refractory (disease does not respond to treatment) disease. Typically, stem cells from a donor are used.