Take Away Points:
- To diagnose chronic lymphocytic leukemia (CLL), there needs to be ≥5000 monoclonal (genetically identical) B-lymphocytes (a type of white blood cell) in the blood for the duration of at least three months. The clonal nature of the circulating B-lymphocytes should be confirmed by flow cytometry (a test that identifies specific surface markers on the cell).
- Small lymphocytic lymphoma (SLL) and CLL are considered to be the same disease (at least since 1994).
- The diagnosis of SLL requires the finding of enlarged lymph nodes and/or an enlarged spleen with less than 5000 B-lymphocytes in the blood. SLL cells show the identical immunophenotype (cell surface fingerprint) as CLL cells. The diagnosis of SLL should be confirmed by lymph node biopsy.
- CLL/SLL is considered both a lymphoma and leukemia.
Hematology in general and CLL specifically are full of jargon and acronyms that can be both overwhelming and daunting. With time and experience, you’ll become familiar with the terminology and acronyms. We will try to explain each medical term the first time it appears in an article, but we will use the true terminology so that you gain comfort and familiarity with the medical terms that you will see in your lab reports and in medical articles. We have provided a list of abbreviations and acronyms as well as a glossary for your reference.
Too Many Clonal B Lymphocytes:
The diagnosis of CLL is dependent on finding on a complete blood count (CBC) an absolute lymphocyte count (ALC) of more than 5,000 or 5,000/microL [5 x 109/L] lymphocytes, specifically more than 5000 clonal B-lymphocytes, present for at least three months.
The important part of your CBC in assessing the amount of cancer cells in your blood is NOT to be found in the report stating “lymphocytes 50.0 given as %” (the # 50.0 is just an example) or even under WBC (white blood cell) with its corresponding number. The most important result worth following is the ALC that can be written different ways such as “Lymphocytes Absolute” or “lymphs #”. Its number is abbreviated to represent thousandths i.e. 20.00 where you can then compare it to a standardized reference range that will vary from lab to lab but is often 1.0 – 4.8 for normal ALC.
CBC Sample Report
|WBC||20 x 10-3/mcl||(4-12 x 10-8/mcl)|
|RBC||6.2 x 10-6/mcl||(5.7-10.5 x 10-6/mcl)|
|HGB||14 g/dl||(9-16 g/dl)|
|MCV||55.9 fl||(40-60 fl)|
|MCH||18.2 pg||(15-20 pg)|
|MCHC||33.5 g/dl||(32-36 g/dl)|
In this sample result one can easily calculate that the 80% of the total WBC of 20,000 are lymphocytes resulting in an absolute lymphocyte count (lymph# or ALC) of 16,000 most consistent with a diagnosis of CLL.
The most important result is highlighted and in bold. The ALC is also the number to follow to assess the progression of the cancer or its response to therapy.
In order to confirm the diagnosis, at one point the blood must be tested to be certain the excess lymphocytes are CLL cells
By the way, the low percent of “neuts” or neutrophils is of no consequence as the absolute count (ANC) was normal.
So in summary, it is not enough to just have a high white blood count or a high percentage of lymphocytes or even an ALC of over 5,000, but we must have more than 5,000 clonal B cells to make the diagnosis. The truth is that when the ALC is significantly high, say 20,000 or higher, odds are very good that the vast majority of the cells are from the CLL clone.
All cancer is clonal.
Lymphocytes are one of the several types of white cells found in our blood stream. They are called lymphocyte because they are the cells found in lymph nodes.
There are three basic types of lymphocytes. NK or natural killers and T cells are different parts of our cell mediated or cellular immune response to infections and cancers. In contrast, our B cells make antibodies that float in the liquid blood and so are said to be part of the liquid or humoral immune system.
By the way, the term humor goes all the way back to the ancient Greeks and Hippocrates who believed that illness was caused by imbalance in the four humors- blood, yellow bile, black bile, and phlegm.
Critical points about CLL:
- Names and classifications of leukemia and lymphoma change
- CLL is a cancer of only B-lymphocytes.
- Cancers of T cells do exist but they should not be called CLL. Since 1997, there is no longer any disease called T –CLL.
- Lymphocytosis (increased lymphocytes) is found in the peripheral blood and bone marrow.
- While only a count of over 5,000 is needed for the diagnosis, a significant proportion of us present with an ALC as high as 100,000.
While CLL is the most common cancer cause of an unexplained high ALC in someone with no symptoms, there are other similar looking blood cancers so it important to nail the diagnosis.
A simple look under the microscope is not confirmatory as our cancer cells are pretty boring and innocent looking.
Confirming The Diagnosis:
To be sure that we are dealing with CLL, it is necessary to see what proteins are found on the cell surface.
These surface markers are called CD for clusters of differentiation and every normal blood cell and type of blood cancer has its own fingerprint of a unique CD pattern. (Truth is there are exceptions and atypical cancers, but that’s beyond the scope of this discussion).
The sophisticated and expensive blood test that tells our doctors what are the surface markers on our cells is called flow cytometry. Flow cytometers can analyze 1000s of cells per second and gives the doctor what is called an immunophenotype, a fingerprint of what proteins are on the cell surface.
The immunophenotype for CLL is listed below. Don’t worry about memorizing this. Even many of the hematologists need to look them up. You can safely skip this whole section, but your doctor can’t skip ordering the flow cytometry.
There is expression of the normal antigens that we could expect with a B-lymphocyte including CD19, CD20, and CD23.
CD52 is another marker found on CLL cells that is also found on both normal B and T cells.
Expression of CD20 is usually but not always weak or dim. Several therapies depend on antibodies attacking CD20. Expression of CD21 and CD24 may or may not be seen, and is not required for diagnosis.
What is unusual and tell us that we have CLL is expression of CD5, an antigen commonly expressed by T cells, but not B-cells.
Our cancer usually has low levels of surface membrane immunoglobulin (antibodies) and only single type of immunoglobulin chain is expressed confirming the clonal nature of these cells.
If you are interested in exploring more of this topic, here is a link to an online tutorial: http://www.bdbiosciences.com/services/training/itf_launch.jsp
It is not necessary to have enlarged lymph nodes to diagnose CLL, but somewhere 50% and 90% of us have enlarged nodes at the time of diagnosis.
Let’s take this moment to emphasize that in most circumstances there is no reason to get a CAT or PET scan to diagnose CLL.
Some of us only have enlarged lymph nodes or an enlarged spleen with no elevated lymphocytes in the blood or bone marrow. The diagnosis is made by a biopsy of the node and then immunophenotyping. This is called Small Lymphocytic Lymphoma or SLL.
For more details on the anatomy discussed in this video and on symptoms in general, please check on the article on symptoms that also includes this short clip.
The finding of greater than 30% CLL cells in the bone marrow or more than 5000 in the blood stream is called CLL.
CLL is considered to be identical to SLL, essentially one disease with different features. The diagnosis is often written as CLL/SLL.
This gets confusing due to the circumstance that CLL/SLL is both a lymphoma (a cancer of lymph nodes) and leukemia (a cancer of white blood cells), but in most cases, there is no clinical significance to these classifications.
There are actually some strange advantages of this dual identity. We patients with CLL/SLL are often eligible for clinical trials and therapies for both leukemia and lymphoma. We also can receive education and support from several lymphoma and/or leukemia organizations such as LLS (Leukemia & Lymphoma Society) (link http://www.lls.org ) and LRF (Lymphoma Research Foundation) (link http://www.lymphoma.org/ ).
A few of us present with CLL in the skin when we have a biopsy for a skin lesion. An enlarged liver or kidney disease is rarely the presenting symptoms leading to diagnosis.
Cytopenias (low blood counts) may be what first brings us to the doctor and lead to the diagnosis. These can be autoimmune diseases where our body tissues are attacked by our own immune system. This can lead to low platelets (necessary for clotting), low red blood cells (they carry oxygen), and low neutrophils (another type of WBC that fights infection).
These autoimmune problems are called:
- Platelets: immune thrombocytopenia (ITP)
- Red Blood Cells: autoimmune hemolytic anemia (AIHA)
- Neutrophils: autoimmune neutropenia
Autoimmune issues will be more fully reviewed in Beyond The Basics.
CLL is mostly commonly suspected when there are too many lymphocytes discovered on a routine blood test done for an unrelated problem. Sometimes it will be one or more lymph nodes that lead to the diagnosis. Other presentations are possible, but less common.
Please remember that the diagnosis is not confirmed until the minimum requirements are met and that must include fingerprinting the lymphocytes to prove that there are all clonal and consistent with B-cell chronic lymphocytic leukemia. More than one patient has been tragically misdiagnosed and offered an inappropriate prognosis and worse, the wrong therapy.
Brian Koffman 3/2/15