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Overview of CLL/SLLBiology BiologyCells of the Blood
There are three types of blood elements: red blood cells, white blood cells and platelets. Each starts out from a single cell type called a stem cell. The human body maintains a fresh supply of cells in the bloodstream by making stem cells in the bone marrow. These stem cells replicate or mature into red blood cells, white blood cells, or platelets depending on the body’s needs at any given time.
White blood cells are the cells in the body that fight infections. Neutrophils and lymphocytes are two of the major subtypes of white blood cells. Lymphocytes include the following:
CLL and SLL BasicsChronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are the same disease with slightly different manifestations. Where the cancerous cells gather determines whether it is called CLL or SLL. When the cancer cells are primarily found in the lymph nodes, lima bean shaped structures of the lymphatic system (a system primarily of tiny vessels found in the body), it is called SLL. When most of the cancer cells are in the bloodstream and the bone marrow, it is called CLL.
CLL is essentially a cancer of the B-lymphocytes. Scientists used to say there were both T-cell CLL and B-cell CLL. However, since 2001, scientists now agree that the usual CLL is a cancer of the B-cells.
Leukemic cells develop because of a change that takes place in the cell’s DNA. Normal (non-cancerous) cells go through stages of growth, division and death. In cancer cells, changes in the DNA (mutations) create cells that keep dividing and/or avoid early or usual cell death (apoptosis). Thus, CLL is usually a disease of accumulation of long lived cells in the body, including the blood, bone marrow, lymph nodes or spleen. Symptoms and DiagnosisSymptoms and Signs
Some findings associated with a diagnosis of CLL are listed below.
Diagnosis
Chronic lymphocytic leukemia (CLL) is diagnosed through a blood test and sometimes biopsies from a lymph node and/or the bone marrow. A blood test will allow physicians to see if there is a higher white count than normal, or any other blood anomaly. What is called a “complete blood count” or CBC, is performed.
A CBC (with “differential”) measures the following:
The differential cell count on a blood smear delineates the proportion of the different types of white cells. It also allows observation of red blood cells and platelets. When CLL is present, future cell counts (CBCs) will show changes, such as an increase in the proportion of lymphocytes in circulation. The pattern of the changes, total counts, or proportions, will help to determine if the disease is progressing.
Many patients do not have symptoms, and the disease may be found through a routine medical exam, leading to a diagnosis of CLL, often through “routine blood work.” People diagnosed with CLL may remain symptom-free for quite some time.
Prognostic Factors
The Role of Classical Predictive Factors in Deciding When to Treat
We will speak a great deal about the newly developing thinking utilizing “predictive factors.” However, doctors consulted in the writing of this report were unanimous in stating that, although they are aware of the new molecular prognostic factors, their decision to treat is still based on the clinical manifestations of the Rai Staging System, a classification developed decades ago. Stage 0 Low Risk Lymphocytosis in blood and marrow only Stage 1, 2 Intermediate Risk Lymphadenopahty (swollen nodes or spleen/liver) Stage 3, 4 High Risk Anemia (low red counts), thrombocytopenia (low platelets) Other classification methods take into account whether there is lymphadenopathy above and below the diaphragm, and which body organs may be involved. To arrive at proper staging, the doctor should consider blood results, biopsies, and body scans. An important method of analysis, flow cytometry, is the measurement of so-called “clusters of differentiation,” antigens/proteins, called CDs. Cells carry these markers on their outer surface, and the type and strength of expression of these markers help doctors determine whether the disease is CLL. The markers classically characteristic of CLL are CD5, CD20, and CD23. The Role of Novel/Molecular Diagnostics in Prognosis
Patients with CLL can have very different experiences before and after diagnosis. Some people may live for a long time without ever requiring therapy, while others may experience a rapid progression of their disease. The healthcare and research communities do not completely understand all the genetic changes present in cancerous cells. However, researchers have been able to identify and link the presence or absence of certain mutations (changes) to how the disease will behave. Techniques have been developed to examine the genes of cells and their possible mutational status.
In the last decade, impressive progress has been made in understanding the genetics of CLL through the development of new diagnostic tests for CLL. Investigators have identified mutations or measurable factors in the bloodstream thought to be of value in predicting how the disease will behave. Having found the same abnormalities in many CLL patients, and observing the course of their disease, scientists establish "prognostic factors." The ultimate value of new prognostic tests for determining treatment is not yet clear. Future and ongoing clinical trials are being conducted to determine whether patients at high risk for disease progression actually benefit from early treatment intervention. A person, for example, with early stage CLL that is demonstrating several unfavorable risk factors may wish to participate in clinical trials designed to measure the benefit of early treatment with chemotherapy in combination with immunotherapy. FISH (fluorescent in-situ hybridization) is a new and useful technique for looking at chromosomal abnormalities, which reflect gene abnormalities. Chromosomes 11, 12, 13 and 17 are of particular interest. Of importance is the presence of the p53 gene, which has an effect on regulating cell death (apoptosis). Hematologists pay particular attention to aberrations (variations from the norm) in the 17th chromosome where the p53 gene is located, since the normal function of p53 is important for the response to chemotherapy. IgVH
The mutational status of a gene known as IgVH helps predict how quickly a person with CLL might progress. Every B-cell rearranges its genes to make specific antibodies to a particular target (antigen) which, for instance, may be on a bacteria. When CLL is derived from cells that undergo the change to make antibodies (mutated genes), an individual will have a more indolent (slow-growing) course of disease. A person with un-mutated (unchanged) IgVH will likely have a more progressive and/or aggressive disease than those with the mutated gene.
ZAP-70
ZAP-70 is a substance involved with cell activation. Researchers have found that the leukemic cells that have ZAP-70 seem to progress faster than those leukemic cells that do not have ZAP-70.
CD-38
CD-38 is a protein antigen attached on the outside of leukemia cells. The presence of CD-38 suggests a faster progression, but scientists still do not completely understand why CD-38 plays a role in CLL.
Summary As scientists continue to research how CLL occurs and progresses, they will continue to develop a better understanding of these factors. Many patients get very anxious about their “progression status” and worry about what this will mean and how long it will be before they need treatment. It is important to remember that at this time most hematologists/oncologists decide when to start treatment for CLL patients based on the clinical (classical) Rai staging, not novel/molecular prognostic factors. Treatment initiation is thus never based on these markers/factors, although they may impact how patients are ultimately treated.
Talking to Your Healthcare Team
When talking to your healthcare team, consider the following:
Considerations on Finding the Best Medical Care Possible
While CLL/SLL has been considered an indolent (slow-growing) or benign illness, it in fact can be quite unpredictable and become quite aggressive.
Many people receive a diagnosis of CLL from their general practioners or local oncologist. Finding a hematologist/oncologist (someone who specializes in treating blood cancers) is critical. Very often, patients travel to cancer centers known for their expertise in treating lymphoma for second opinions and return home for treatment. You are your own best advocate. Taking control of your care requires you to learn about CLL, from this website and other sources, speak to the experts and make informed decisions about tests and treatment options. Get smart about CLL. You should be your own best advocate.
The CIG website also provides information about available treatments for CLL/SLL and upcoming educational programs. |
