CLL

Chronic Lymphocytic
Leukemia
LEUKEMIA LYMPHOMA MYELOMA
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A Message from John Walter
President and CEO of The Leukemia & Lymphoma Society
The Leukemia & Lymphoma Society (LLS) is committed to bringing you

the most up-to-date blood cancer information. We know how important
it is for you to have an accurate understanding of your diagnosis,
treatment and support options. With this knowledge, you can work
with members of your oncology team to move forward with the hope of
remission and recovery.
Our vision is that one day the great majority of people who have been
diagnosed with chronic lymphocytic leukemia (CLL) will be cured or
will be able to manage the disease with good quality of life. We hope that
the information in this booklet will help you along your journey.
LLS is the world’s largest voluntary health organization dedicated to

funding blood cancer research, education and patient services. Since its
founding in 1949, LLS has invested more than $600 million in research
specifically targeting blood cancers. We will continue to invest in research
for cures and in programs and services that improve the quality of life of
people who have CLL and their families.
We wish you well.
John Walter
President and CEO
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Table of Contents
Introduction 3
Normal Blood and Marrow 3
The Lymphatic System 6
Leukemia 6
Chronic Lymphocytic Leukemia 7
Symptoms and Signs 9
Diagnosis 10
Treatment Planning 12
Treatment 15
Complications: CLL or CLL Treatment 19
Clinical Trials 21
Treatment Response and Follow-up 23
Related Diseases 25
Social and Emotional Effects 28
Glossary 31
Resources 44
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Introduction
This booklet provides information about chronic lymphocytic leukemia (CLL) for
patients and their families. Brief descriptions of normal blood and bone marrow
and the lymphatic system are provided to help readers better understand the
CLL-specific information in the booklet.
An estimated 85,713 people are living with CLL, and 15,490 people are expected
to be diagnosed with CLL in the United States in 2009. Physicians have learned
a great deal in the last few decades about CLL. In the last several years, new
therapies have been developed, and outcomes for people living with CLL are
steadily improving. Researchers around the world continue to strive to find a
cure for CLL.
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not engaged in providing medical or other professional services.
Normal Blood and Marrow

Blood is composed of plasma and cells suspended in plasma. The plasma is largely
made up of water in which many chemicals are dissolved. These chemicals include
• Proteins (such as albumin and blood-clotting proteins made in the liver, and
erythropoietin, which is made in the kidneys)
• Hormones (such as thyroid hormone and cortisol)
• Minerals (such as iron and magnesium)
• Vitamins (such as folate and vitamin B12)
• Electrolytes (such as calcium, potassium and sodium)
• Antibodies, including those we develop from vaccinations (such as poliovirus
antibodies, which are made by normal plasma cells in the bone marrow).
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The cells suspended in plasma include red cells, platelets and white cells
(neutrophils, monocytes, eosinophils, basophils, and lymphocytes).
• The red cells make up a little less than half the volume of the blood. They are filled
with hemoglobin, the protein that picks up oxygen in the lungs and delivers it to the
cells all around the body; hemoglobin then picks up carbon dioxide from the body’s
cells and delivers it back to the lungs, where it is removed when we breathe out.
• The platelets are small cells (one-tenth the size of red cells) that help stop
bleeding at the site of an injury in the body. For example, when a person has a
cut, the vessels that carry blood are torn open. Platelets stick to the torn surface of
the vessel, clump together and plug up the bleeding site with the help of blood-
clotting proteins such as fibrin and electrolytes such as calcium. Later, a firm clot
forms. The vessel wall then heals at the site of the clot and returns to its normal
state. The platelets also release growth factors that stimulate wound repair and
new blood vessel formation.
• T
he neutrophils and monocytes are white cells. They are called “phagocytes”
(eating cells) because they can ingest bacteria or fungi and kill them. Unlike
the red cells and platelets, the monocytes can leave the blood and enter the
tissue, where they can attack the invading organisms and help combat infection.
Eosinophils and basophils are types of white cells that respond to allergens or
parasites.
• A
lymphocyte is another type of white cell. Most lymphocytes are found in
the lymph nodes, the spleen and the lymphatic channels, but some enter the
blood. There are three major types of lymphocytes: T lymphocytes (T cells), B
lymphocytes (B cells) and natural killer (NK) cells. These cells are a key part of
the immune system.
Marrow is a spongy tissue where blood cell development takes place. It occupies
the central cavity of bones. In newborns, all bones have active marrow. By the time
a person reaches young adulthood, the bones of the hands, feet, arms and legs no
longer have functioning marrow. The spine (vertebrae), hip and shoulder bones,
ribs, breastbone and skull contain the marrow that makes blood cells in adults.
The process of blood cell formation is called “hematopoiesis.” A small group of
cells, the stem cells, develop into all the blood cells in the marrow by the process of
differentiation (see Figure 1 on page 5).
In healthy individuals, there are enough stem cells to keep producing new blood cells
continuously. Blood passes through the marrow and picks up the fully developed and
functional red and white cells and platelets for circulation in the blood.
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Blood Cell & Lymphocyte Development
STEM CELLS
Multipotential Multipotential
Hematopoietic Cells Lymphocytic Cells
Differentiate & Differentiate &

mature into six types mature into three
of blood cells types of lymphocytes
Red Cells Basophils T Lymphocytes

Neutrophils Monocytes B Lymphocytes
Eosinophils Platelets Natural Killer Cells
Figure 1. This figure depicts an abbreviated diagram of the process of hematopoiesis. This process
involves the development of functional blood and lymphatic cells from stem cells.
Some stem cells also enter the blood and circulate. They are present in such small
numbers that they cannot be counted or identified by standard blood count tests.
Their presence in the blood is important because they can be collected by a special
technique. There are also methods to induce more stem cells to leave their home
in the marrow and circulate in the blood, allowing a greater stem cell collection
to occur. If enough stem cells are harvested from a compatible donor, they can be
transplanted into a recipient.
Stem cell circulation, from marrow to blood and back, also occurs in the fetus. After
birth, placental and umbilical cord blood can be collected, stored and used as a
source of stem cells for transplantation.
In summary, blood cells are made in the marrow. When the cells are formed and
functional, many of them leave the marrow and enter the blood. The red cells and
the platelets carry out their respective functions of delivering oxygen and plugging up
injured blood vessels throughout the body. The white cells (neutrophils, monocytes,
eosinophils, basophils and lymphocytes) enter the tissue (for example, the lungs) to
combat infections, such as pneumonia, and perform other immune functions.
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The Lymphatic System
The lymphatic system is an important part of the body’s immune system. The lymphatic
system is closely related to the blood cell-forming system in the marrow.
Lymph nodes are part of the lymphatic system. Most lymphocytes (a type of white
cell) are found in the lymph nodes. They are also found in other parts of the lymphatic
system, such as the skin, spleen, tonsils and adenoids, the intestinal lining and,
in young people, in the thymus. Lymphocytes circulate through channels called
“lymphatic vessels” that connect lymph nodes throughout the body. The lymphatic
vessels collect into large ducts and then the ducts empty into blood vessels. The
lymphocytes enter the blood through these ducts.
The three main types of lymphocytes are
• B lymphocytes (B cells), which make antibodies in response to invading bacteria,

viruses, or other microbes. B lymphocytes are present in the marrow.
• T lymphocytes (T cells), which have several functions, including helping B

lymphocytes to make antibodies against invading microbes. An antibody attaches to
an invading microbe. A white cell then recognizes the antibody and pulls it into the
cell with the attached microbe. The white cell can then kill the microbe.
• Natural killer (NK) cells, which attack virus-infected cells without requiring an
antibody or other assistance.
Leukemia
Leukemia is a cancer of the marrow and blood. The four major types of leukemia
are chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL),
chronic myelogenous leukemia (CML), and acute myelogenous leukemia (AML).
Leukemia is called “lymphocytic” (or “lymphoblastic”) if the cancerous change

takes place in a type of marrow cell that forms lymphocytes. Leukemia is called
“myelogenous” (or “myeloid”) if the cell change takes place in a type of marrow cell
that would normally go on to form red cells, some kinds of white cells and platelets.
Chronic leukemia is a slow-growing blood cancer that permits the growth of

greater numbers of more developed cells. In general, these more mature cells
can carry out some of their normal functions. Acute leukemia is a more quickly
growing disease that affects unformed cells or cells that are not yet fully developed.
These immature cells cannot carry out their normal functions.
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The four main types of leukemia are further classified into subtypes that are based on
specific features of cells. Knowing the subtype of the patient’s disease may help the
physician to assess how quickly the disease may progress. The subtype is important
because the treatment approach may vary according to the disease subtype.
Lymphocytic Leukemia and Lymphoma. The World Health Organization (WHO)

includes “lymphocytic leukemias” and “lymphoma” within one classification.
Each of these cancers is the result of a change to a cell that was destined to be a
lymphocyte. However, lymphocytic leukemia and lymphoma originate in different
parts of the body. Lymphocytic leukemia develops in the lymphatic tissue within
the marrow. Lymphoma begins in a lymph node, or another lymphatic structure in
the skin, the gastrointestinal tract, or some other site in the body.
Acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL)

are the two major types of lymphocytic leukemia. It should be noted that CLL
and small cell lymphocytic lymphoma (SLL) are similar diseases with regard to
incidence, signs and symptoms, disease progression and treatment. The leukemic
lymphocytes and tissue abnormalities that are observed in people with SLL are
identical to those observed in patients with CLL. However, in people with SLL,
there is more lymph node and lymphoid tissue involvement and less marrow
and blood involvement; in people with CLL, the marrow and blood are more
strikingly affected.
More information about leukemia and lymphoma can be found in the free LLS
publications Understanding Leukemia and The Lymphoma Guide—Information
for Patients and Caregivers.
Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) results from an acquired (not present at birth)
change (mutation) to the DNA of a single marrow cell that develops into a lymphocyte.
In 95 percent of people with CLL, the change occurs in a B lymphocyte. In the other
5 percent of people with CLL, the cell that transforms from normal to leukemic has
the features of a T lymphocyte or an NK cell. Thus, any of the three major types of
lymphocytes (T cells, B cells or NK cells) can undergo a malignant transformation that
causes diseases related to B-cell CLL (see Related Diseases on page 25).
Scientists do not yet understand what causes this change. Once the marrow cell
undergoes the leukemic change, it multiplies into many cells. CLL cells grow
and survive better than normal cells; over time, they crowd out normal cells.
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The result is the uncontrolled growth of CLL cells in the marrow, leading to
an increase in the number of CLL cells in the blood. The leukemic cells that
accumulate in the marrow in people with CLL do not impede normal blood
cell production as extensively as is the case with acute lymphocytic leukemia.
This is an important distinction: It is the reason for the generally less severe
early course of CLL.
CLL takes different forms. Some people have disease that is slow-growing.
People with minimal changes in their blood cell counts (an increase in the
number of blood lymphocytes and little or no decrease in the number of red
cells, normal neutrophil and platelet counts) may remain stable for years. Other
people with CLL have a faster-growing form of the disease—the CLL cells
accumulate in the bone marrow and blood, and there is a significant decrease
in the numbers of red cells and platelets.
People with faster-growing CLL may have
•E
nlarged lymph nodes that can lead to compression of neighboring organs.
For example, enlarged lymph nodes in the abdomen can interfere with the
functions of the gastrointestinal tract and/or the urinary tract.
•A
severe immunoglobulin deficiency, sometimes coupled with a low
neutrophil count, which can lead to recurrent infections.
Causes and Risk Factors. CLL has generally not been associated with any
environmental or external factors. However, the Institute of Medicine of
the National Academy of Sciences issued a report “Veterans and Agent
Orange: Update 2002,” which concluded that there was “sufficient evidence
of an association” between herbicides used in Vietnam and CLL. For
more information from the US Department of Veterans Affairs see
www1.va.gov/AgentOrange or call (800) 827-1000.
First-degree relatives of patients with CLL are three to four times more likely
to develop CLL than people who do not have first-degree relatives with the
disease. However, the risk is still small. For example, the 60-year-old sibling
or child of someone with CLL would have three to four chances in 10,000
of developing the disease, compared with the one chance in 10,000 for a
60-year-old person without a family history of the disease.
Incidence. CLL is more common in people who are 60 years and older (see
Figure 2 on page 9). The incidence of the disease increases from one per
100,000 in individuals aged 30 to 34 years to more than 30 per 100,000 in
individuals aged 80 and older.
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Chronic Lymphocytic Leukemia
Age-Specific Incidence Rates 2002-2006
Incidence (No. per 100,000) 35
30
25
20
15
10
5
0
<1 1-4 5-9 0-14 5-19 0-24 5-29 0-34 5-39 0-44 5-49 0-54 5-59 0-64 5-69 0-74 5-79 0-84 85+
1 1 2 2 3 3 4 4 5 5 6 6 7 7 8
Age (years)
Figure 2. The horizontal axis shows the age at diagnosis, in 5-year age-groups, of people in the United
States who develop CLL. The vertical axis represents the number of new cases of CLL per 100,000
people in each 5-year age-group. The risk for developing CLL becomes measurable in the 30- to 34-
year age-group (0.1 per 100,000) and increases in succeeding decades. Source: Horner MJ, Ries LAG,
Krapcho M, Neyman N, Aminou R, Howlader N, Altekruse SF, Feuer EJ, Huang L, Mariotto A, Miller
BA, Lewis DR, Eisner MP, Stinchcomb DG, Edwards BK (eds). SEER Cancer Statistics Review, 1975-
2006, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2006/, based on
November 2008 SEER data submission, posted to the SEER web site, 2009.
Symptoms and Signs

CLL symptoms usually develop over time. Early in the course of the disease, CLL
often has little effect on a person’s well-being. Some people with CLL do not have
any symptoms. The disease may be suspected because of abnormal results from
blood tests that were ordered either as part of an annual physical or a medical
examination for an unrelated condition. An elevated white cell (lymphocyte) count
is the most common finding that leads a physician to consider a CLL diagnosis.
People with CLL who do have symptoms may tire more easily, and/or may feel
short of breath during day-to-day physical activities—as a result of anemia (low red
cell count). They may lose weight because of decreased appetite and/or increased
use of energy. The lymph nodes and spleen may become enlarged as a result of
an accumulation of CLL cells (leukemic lymphocytes). Infections of the skin,
lungs, kidneys or other sites may occur as result of low immunoglobulin levels and
decreased neutrophil counts.
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Diagnosis
Blood Cell Count and Examination. The diagnosis of CLL is usually evident
from the results of blood cell counts and an examination of blood cells. A person
with CLL will have increased numbers of lymphocytes. Low platelet counts and
low red cell counts may also be present; these counts are usually only slightly
decreased in the early stage of the illness.
Bone Marrow Examination. A bone marrow aspiration and biopsy generally

are not needed to make a diagnosis of CLL. However, these tests are usually
recommended before treatment begins—the test results provide baseline data that
can be used later on to evaluate the effects of therapy. Repeat marrow biopsies are
helpful in distinguishing disease versus treatment-related causes of low blood cell
counts that do not improve within an expected period of time after treatment.
In people with CLL, a bone marrow examination will show an increase in the
number of lymphocytes in the marrow and often a decrease in the number of
normal marrow cells. The bone marrow biopsy results will also show one of four
patterns characteristic of CLL: nodular, interstitial, mixed or diffuse.
Immunophenotyping. “Immunophenotyping” of lymphocytes is an important

process used to diagnose CLL, and other types of leukemia and lymphoma, by
comparing the cancer cells to normal immune cells. The test results indicate
whether or not the person’s lymphocytes are monoclonal (derived from a
single cancer cell). This is important because it distinguishes leukemia from the
infrequent increase in adults of blood lymphocytes from a noncancerous origin.
This test is especially important if the number of lymphocytes in the blood is only
slightly elevated. Immunophenotyping also determines whether the CLL cells are
from a change in either B-cell or T-cell development (see Figure 3 on page 11).
Most people with CLL have the B-cell type. For information about T-cell CLL see
Related Diseases on page 25.
Immunophenotyping is done with an instrument called a “flow cytometer.” A

sample of cells from blood or marrow can be tagged with an antibody that is
specific for a site on the cell surface. The cells go through the flow cytometer,
passing through a laser beam; if they have the antibody-specific surface feature,
the cells light up and they are counted.
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Lymphocyte Development
Stem Cells
Other Blood
Cells
Lymphocyte Progenitor
Early
Specialized
Lymphocytes
Fully
Developed
Specialized
Lymphocytes
B Cells T Cells NK Cells
Figure 3. Mutation of DNA can occur when the early specialized lymphocytes are formed or after
the lymphocyte progenitor has differentiated into one of the three specific types of lymphocytes. The
leukemic cells may be principally B cells, T cells or NK cells. Most patients have a B-cell type of CLL.
Immunoglobulin Levels. The measurement of the concentration of

immunoglobulins (gamma globulins) in the blood is another important test.
Immunoglobulins are proteins called “antibodies” that are made by B cells in
healthy individuals to protect the body from infection. CLL cells do not make
effective antibodies. CLL cells also interfere with the ability of the remaining
normal lymphocytes to make antibodies. As a result, people with CLL often
have low levels of immunoglobulins, which increases their risk of getting
infections.
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Treatment Planning
Staging. Staging for CLL helps physicians to both assess how the disease is
expected to progress and also to develop a treatment plan. Staging systems for
CLL take into account
• The elevation of blood and marrow leukemic lymphocyte counts

• The size and distribution of lymph nodes
• The spleen size
• The degree of anemia and the extent of decreased blood platelet counts.
Table 1. Commonly Used CLL Staging Systems

Rai Staging System Binet Staging System
Stage and Signs at Diagnosis Stage and Signs at Diagnosis
Low Risk—0 A
Abnormal increase in the number of bnormal increase in the number
A
lymphocytes in the circulating blood of lymphocytes in the circulating
and marrow blood and <3 areas of palpable
enlarged lymphoid tissue
Intermediate Risk—I & II B
Abnormal increase in the number of bnormal increase in the number
A
lymphocytes in the circulating blood of lymphocytes in the circulating
and marrow and enlarged lymph nodes blood and >3 areas of palpable
or enlarged lymphoid tissue
Abnormal increase in the number of
lymphocytes in the circulating blood
and marrow and enlarged spleen
and/or liver
High Risk—III & IV C
Abnormal increase in the number of ame as B with anemia
S
lymphocytes in the circulating blood (hemoglobin <11 g/dL in men or
and marrow and anemia (hemoglobin hemoglobin <10 g/dL in women)
<11 g/dL) or low platelet count (platelets
or <100,000/μL)
Abnormal increase in the number of
lymphocytes in the circulating blood
and marrow and low platelet count
(platelets <100,000/μL)
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Chromosomal Changes. Certain chromosomal changes can help the physician to
identify those people with CLL who may benefit from closer medical
follow-up or certain types of therapy. About half of the people with CLL have
CLL cells with chromosomal abnormalities when tested with a method called
“G-banding karyotyping.” About 80 percent of the people with CLL have
chromosomal abnormalities when tested with a method called “fluorescence in
situ hybridization (FISH).” The following examples are some of the more common
chromosomal abnormalities:
Del 13q Deletions on the long arm of chromosome 13 (del 13q) are
the most common. Del 13q with no other chromosomal
abnormalities is associated with a relatively more favorable
outcome.
Trisomy 12 About 10 to 20 percent of patients have CLL cells with

three copies of chromosome 12 (trisomy 12) instead of the
expected two chromosomes. Trisomy 12 is associated
with intermediate-risk CLL. Trisomy 12 with other
chromosomal abnormalities is associated with a higher
risk than trisomy 12 alone.
Del 11q Up to 20 percent of people with CLL have deletions in

CLL cells in the long arm of chromosome 11 (del 11q). The
proportion of CLL patients with del 11q tend to be younger
and have high-risk disease.
Chromosome 14 Structural abnormalities of chromosome 14 or chromosome 6

or in CLL cells also indicate higher-risk disease.
Chromosome 6
Del 17p About 10 percent of people with CLL have deletions in the
short arm of chromosome 17 (del 17p). The critical gene in
this region that is typically deleted is TP53. People who have
CLL with del 17p tend to have higher-risk disease and usually
do not respond as well to standard initial therapy.
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Other factors may be signs of faster-growing disease (higher-risk CLL) and
indicate the need for closer follow-up with the physician. For example:
Blood lymphocyte doubling People with CLL whose lymphocyte number

doubles in one year have higher-risk CLL and
need closer follow-up; a lymphocyte number that
remains stable indicates a relatively lower risk.
B2M A higher level of serum beta 2-microglobulin,

(B2M) a protein that is shed from CLL cells,
is associated with a greater extent of disease.
Several studies have found that B2M and
other serum markers, such as CD23, may
help predict survival or progression-free
survival. Tests for these markers need to be
standardized, and further study in clinical trials
is needed to evaluate their relative value in
managing the treatments of people with CLL.
CD38 CD is an abbreviation for “cluster designation,”

a term used with a number to identify a specific
molecule on the surface of an immune cell. The
expression of CD38 on CLL cells may be an
indicator of higher-risk CLL.
Unmutated IgHv The unmutated immunoglobulin heavy chain

variable region gene (IgHv) suggests the
likelihood of higher-risk disease
ZAP-70 ZAP-70 (zeta-associated protein 70), when

increased, may be associated with higher-risk
disease.
It should be noted that further study in clinical trials is needed to standardize the
assessment of ZAP-70 and also to determine how Zap-70, CD38 expression and
unmutated IgHv should affect the management of people with CLL.
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Treatment
Current therapies do not offer patients a cure for CLL, but there are treatments that
help manage the disease. Treatments for CLL include
• Watch and wait

• Single or combination drug therapy
• Blood cell growth factors
• Radiation therapy
• Splenectomy
• Treatment in a clinical trial
- Drug therapy with new drugs or new drug combinations
- High-dose chemotherapy and allogeneic stem cell transplantation.
The goals of CLL treatments are to
• Slow the growth of the CLL cells

• Provide long periods of remission (when there are no signs of CLL and/or people
feel well enough to go about their day-to-day activities)
• Help people to feel better if they have infections, fatigue or other symptoms.
Some people with CLL can be managed with a watch and wait approach for years
before the disease progresses. The decision to treat a person with CLL is based on a
number of factors (see Table 2).
A person with CLL is usually treated by a hematologist or an oncologist. People

are advised to consult with a physician who specializes in treating patients with
leukemia and to discuss their most appropriate treatment options—including
whether or not participation in a clinical trial is recommended.
Table 2. Some Factors That Influence

the Decision to Treat Patients With CLL*
Relatively rapid increase of blood lymphocyte counts
Enlarging lymph nodes
Enlarging spleen
Worsening anemia
Falling platelet count
*Several of these factors are often present at the same time.
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Watch and Wait. People with CLL who have minimal changes in their blood counts
and no symptoms are usually managed with observation alone. This approach
includes medical examinations and periodic testing to determine whether the
disease is stable or beginning to progress. People with CLL being treated with
a watch and wait approach are counseled by their physicians to seek medical
assistance if they develop fevers or other signs of infection or illness. When, or if,
the disease begins to progress, active treatment is started.
People are often concerned when they receive a diagnosis of CLL and then learn
that they will not begin treatment right away. It is important to know that the
watch and wait approach is the current standard of care for people with CLL who
have minimal changes in their blood counts and no symptoms. Many studies have
compared the watch and wait approach to an early treatment approach for people
with low-risk CLL. To date, no benefits of early treatment for people with low-risk
CLL have been shown. Several studies have confirmed that the use of alkylating
agents in patients with early-stage disease does not prolong survival. Deferred
treatment versus early treatment for people with CLL who are symptom-free is an
area of ongoing study in clinical trials.
Drug Therapies
The following therapies may be used to treat people with newly diagnosed CLL,
relapsed CLL or refractory CLL (see Relapsed or Refractory CLL on page 18).
Patients who have intermediate- and high-risk disease are usually treated with
chemotherapy and/or monoclonal antibody therapy. The choice of recommended
treatment generally depends on the patient’s overall health status and the stage of
his or her disease. Age may be a factor for certain types of therapy.
Chemotherapy. Fludarabine (Fludara®) is considered to be one of the most effective

types of chemotherapy for CLL. Drug combinations, including fludarabine and
cyclophosphamide (Cytoxan®)—FC; fludarabine and rituximab (Rituxan®)—FR;
and fludarabine, cyclophosphamide and rituximab—FCR—are often used to
treat patients with intermediate- and high-risk CLL. Studies comparing treatment
with fludarabine alone to treatment with FC, or to treatment with various FCR
regimens, have shown that combination treatments significantly improve the
frequency of complete response in previously untreated people with CLL (see
Treatment Response and Follow-up on page 23). Additional studies in clinical
trials are needed to determine which patients will benefit from FCR versus other
CLL treatments. In addition, treatments combining fludarabine with other drugs are
currently being studied in clinical trials.
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Bendamustine (Treanda®) is another type of chemotherapy that is approved for
the treatment of CLL. Combinations of bendamustine and other drugs, including
rituximab and lenalidomide (Revlimid®), are currently being studied in clinical
trials for the treatment of people with CLL.
Monoclonal Antibody Therapy. Monoclonal antibodies are proteins that are

bioengineered in the laboratory. Each monoclonal antibody therapy is designed to
recognize a specific molecule on a cell. The monoclonal antibody therapy targets
the molecule and attaches to the cell, causing the cell to die.
The monoclonal antibody therapies rituximab (Rituxan) and alemtuzumab

(Campath®) are used to treat people with CLL (see Table 3 on page 18). Rituximab
targets CD20 on the CLL cell’s surface; alemtuzumab targets CD52. Alemtuzumab is
approved as a single agent for CLL treatment. Both rituximab and alemtuzumab have
been very effective in treating many people with CLL.
These therapies continue to be studied in clinical trials. Other new monoclonal

antibodies, such as ofatumumab (Arzerra®) and lumiliximab are also being studied
in clinical trials, either alone or combined with chemotherapy, as treatment for
previously untreated patients and for patients with refractory or relapsed CLL
(see Clinical Trials on page 21).
Most chemotherapy affects normal tissue cells as well as CLL cells. Monoclonal
antibody therapy may affect some normal lymphocytes but spare most other
cells. Even though the infusion of a monoclonal antibody into a patient’s vein
may cause a short period of fever, chills or low blood pressure, generally people
experience less troubling side effects with monoclonal antibody therapy than with
chemotherapy. The drugs most commonly used to treat CLL are shown in Table 3
on page 18.
Blood Cell Growth Factors. Treatment for CLL may include administering blood
cell growth factors to improve low red cell counts or low white cell counts.
Treatment with blood cell growth factors may help people with CLL to tolerate
the side effects of higher doses of chemotherapy (see Complications: CLL or CLL
Treatment on page 19).
Radiation Therapy. Radiation is sometimes used to shrink large lymph node

masses or masses in locations that interfere with the function of a neighboring
body part, such as the kidney, the gastrointestinal tract or the throat.
Splenectomy. CLL cells can accumulate in the spleen and become problematic in
some people with CLL. Surgical removal (splenectomy) of a very enlarged spleen
may improve blood cell counts. This approach is used selectively because it is only
beneficial if the patient’s spleen is affected by CLL.
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Table 3. Some Drugs Used to Treat Chronic
Lymphocytic Leukemia
Chemotherapy Monoclonal Antibody Therapy

Bendamustine (Treanda®) Alemtuzumab (Campath®)
Chlorambucil (Leukeran®) Lumiliximab*
Cladribine (Leustatin®) Ofatumumab (Arzerra®)*
Cyclophosphamide (Cytoxan®) Rituximab (Rituxan®)*
Doxorubicin (Adriamycin®)
Fludarabine (Fludara®) Other Drugs
Prednisone Flavopiridol [kinase inhibitor]*
Vincristine (Oncovin®) Lenalidomide (Revlimid®)*
[immunomodulator]
*Under study in clinical trials
Relapsed or Refractory CLL. “Relapsed CLL” is the term for disease that
responded to therapy but, after six or more months, stopped responding.
“Refractory disease” is the term for CLL that does not result in a remission (but
may be stable) or disease that gets worse within six months of the last treatment.
People who are treated for relapsed or refractory CLL often have good quality
years of remission after more treatment. Treatment guidelines for people with
relapsed CLL are generally the same as treatment for newly diagnosed people.
People who have refractory CLL with a short time to progression after the first
treatment and/or CLL cells with del 17p often do not respond to standard
chemotherapy. These people are advised to speak to their physicians about
whether or not treatment in a clinical trial is a good option for them. Investigative
clinical protocols for drug therapies or allogeneic stem cell transplantation may
offer appropriate treatment options (see Clinical Trials on page 21).
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Complications: CLL or CLL Treatment
Infection. Infections are a common complication for people with CLL.
A higher risk of infections is caused by
• The inability of the person’s CLL cells to make antibodies needed to fight
infections
• The effect of chemotherapy, which causes reduced cell counts for certain
infection-fighting white cells in the blood, specifically neutrophils and monocytes.
Antibiotic therapy is usually required to treat bacterial or fungal infections during

the course of the disease. People who get recurrent infections may also receive
injections of immunoglobulin (gamma globulin) on a regular basis to correct the
immune deficiency.
CLL-related low blood counts are often efficiently corrected by CLL therapy.
However, the use of white cell growth factors may benefit patients who experience
prolonged low white cell counts after treatment. Examples of white cell growth
factors are
• Granulocyte-colony stimulating factor (G-CSF) [filgrastim (Neupogen®) or

pegfilgrastim (Neulasta®)] that can increase the number of neutrophils
• Granulocyte-macrophage colony-stimulating growth factor (GM-CSF)

[sargramostim (Leukine®)] that can increase the number of neutrophils
and monocytes.
Anemia. Anemia (low numbers of red cells) is a common side effect of

chemotherapy. Some people with CLL may need blood transfusions or
administration of red cell growth factors to increase the red cell count. Examples
of red cell growth factors are Aranesp® (darbepoetin alfa) and Procrit® (epoetin
alfa). People with CLL should discuss with their physicians the risks and benefits of
treatment using red cell growth factors.
Richter Transformation. In about 3 percent of people with CLL, the disease

transforms into an aggressive lymphoma because of a change in the characteristics
of the CLL cells. This pattern is referred to as a “Richter transformation.” People
with this type of CLL may have significantly enlarged lymph nodes, and may have
fevers and weight loss. Tumors of lymphocytes may also develop in parts of the body
other than the lymph nodes.
Prolymphocytes. About 15 percent of people with CLL have leukemia cells that are
a mix of lymphocytes and another type of white cell, called a “prolymphocyte”
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(see Figure 4, Panel D). Most people with this type of CLL follow a similar
course to that of other people with CLL. However, for a relatively small subset of
patients with this type of CLL, the blood cells may become mainly composed of
prolymphocytes; the spleen may enlarge further, and the disease may become less
responsive to treatment. In these cases, individuals are encouraged to talk to their
physicians about the potential benefits of treatment in a clinical trial.
Lymphocytes
A B
C D
Figure 4. Panel A shows a normal lymphocyte in the blood film of a healthy person. Panel B shows
the increased frequency of lymphocytes in the blood film of a patient with CLL. Panel C shows the
appearance of large granular lymphocytes in a patient with large granular lymphocytic leukemia (the
arrows point to the cluster of granules in the cells), and Panel D shows the cells of prolymphocytic
leukemia, which are larger than those in Panels A and B and have a light area in their nucleus, called a
“nucleolus” (see arrow). This structure in the nucleus is a sign of a more immature or primitive cell.
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Autoimmune Hemolytic Anemia. Some people with CLL produce a type of
antibody that works against their own cells. These “autoantibodies” are usually
directed against the patient’s red cells, which causes them to be removed rapidly
from the blood. This condition, called “autoimmune hemolytic anemia,” can
worsen the effects of already low red cell counts. The “antiglobulin test” or
“Coombs’ test” is used to identify the autoantibodies. Less often, the antibody
works against the platelets. This condition, called “immune thrombocytopenia,”
results in significantly decreased platelet counts. The drugs prednisone and
cyclosporine are sometimes used to treat autoimmune hemolytic anemia and
immune thrombocytopenia.
Second Cancers. People with CLL have a higher risk than the general population
of developing a second cancer. The second cancers that are seen most frequently
are melanoma, soft tissue sarcoma, colorectal cancer, lung cancer, squamous
cell skin cancer and basal cell carcinoma. The recurrence rate of basal cell
carcinoma after treatment is also higher for people with CLL compared to the
general population. The rate of myeloma is also 10 times higher in people with
CLL than in the general population. Both treated and untreated people with CLL
can develop acute myelogenous leukemia or myelodysplastic syndromes. Further
evaluation is needed to determine whether treatment with fludarabine increases
the risk of second cancers. However, treatment with alkylating agents may
increase the risk for second cancers in some cancer survivors.
Clinical Trials
Clinical trials are conducted under rigorous guidelines to help physicians determine
the benefits of new treatments and what, if any, side effects can be expected. In
these trials, new drugs, new types of targeted therapies and new approaches to stem
cell transplantation are being explored in order to bring people with CLL better
treatments and improve their quality of life. New approaches to treatment, many of
which are being supported by LLS research programs, hold the promise of increasing
the rate of remission and finding a cure for CLL.
New Drug Treatments. New drugs and new combinations of drugs are being studied
in clinical trials. The objective is to develop more effective treatments for CLL. This
is an ongoing process as pharmaceutical companies, in cooperation with academic
health centers, introduce new drugs into clinical trials. Some clinical trials also study
the effect of existing drugs given in different doses and on different schedules.
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Specific new drug therapies under study in clinical trials for people with CLL
include
Ofatumumab (Arzerra). Ofatumumab is an investigational, monoclonal

antibody that targets CD20. CD20 is a key target in CLL therapy because it is
expressed on most B cells in people with CLL. The FDA’s Oncologic Drugs
Advisory Committee (ODAC) has determined that data from clinical trials for
Arzerra are reasonably likely to indicate that the drug will benefit people with
CLL whose disease is refractory to fludarabine (Fludara) and alemtuzumab
(Campath).
Lumiliximab. Lumiliximab is an antibody that targets CD23 on the surface

of CLL cells. It is being studied in phase II and phase III clinical trials in
combination with fludarabine, cyclophosphamide and rituximab (FCR) to see
if it enhances the activity of FCR for treatment of patients with relapsed CLL.
Flavopiridol. Flavopiridol is being studied in people with high-risk genetic

features whose CLL has responded to few, if any, standard treatments. It is
being studied to treat CLL or prolymphocytic leukemia arising from CLL that
is refractory to fludarabine.
Lenalidomide (Revlimid). Lenalidomide is an oral drug that is used to treat

patients with myeloma. It is an immunomodulatory drug that stimulates a
person’s own immune system to attack cancer cells. This drug is being evaluated
in several CLL trials, including a phase III study, to determine if lenalidomide,
given as a maintenance therapy, is safe and effective in further improving the
quality and duration of the response to treatment. This study will compare
the effects of lenalidomide with the effects of a placebo. Lenalidomide is also
being studied as a possible treatment for people with CLL following second-
line therapy. Other studies include lenalidomide, fludarabine and rituximab
combined for minimally treated and untreated CLL patients, and lenalidomide,
fludarabine and cyclophosphamide combined for patients with advanced
relapsed or refractory CLL.
Improvements in Stem Cell Transplantation. New procedures for allogeneic

stem cell transplantation are being studied in clinical trials. Research teams are
now trying novel ways to reduce the toxicity of transplantation and make it a
possible therapy for more people with CLL.
Allogeneic stem cell transplantation is an investigational treatment option for

people with high-risk CLL that has not responded to other standard therapies.
It may be an appropriate therapy for carefully selected younger people with CLL
who can be matched with a stem cell donor.
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A modified form of allogeneic stem cell transplantation called a “reduced-
intensity” or “nonmyeloablative” allogeneic stem cell transplantation may
be another transplant option for CLL patients who do not respond to other
treatments. Patients being prepared for a reduced-intensity transplant receive lower
dosages of chemotherapy drugs and/or radiation in preparation for the transplant,
compared to the dosages given to patients receiving an allogeneic transplant.
Immunosuppressive drugs are used to prevent rejection of the donor stem cells,
and the engraftment of donor immune cells may allow these cells to attack the
CLL cells (called “graft-versus-tumor effect”). The theory being tested with a
reduced-intensity transplant is that by undergoing less-toxic procedures prior to the
stem cell transplant, the body is better able to withstand the infusion of donor cells.
However, full donor engraftment would still take place, and the desired
graft-versus-tumor effect would still occur.
The Information Resource Center at LLS offers guidance on how patients

can work with their physicians to find out if a specific clinical trial is an
appropriate treatment option. Information Specialists conduct individualized
clinical trial searches for patients, family members and healthcare
professionals. This service can be accessed by calling (800) 955-4572 or by
visiting www.LLS.org/clinicaltrials.
Treatment Response and Follow-up

Treatment Outcomes
Treatment outcomes for people with CLL vary widely, and expected outcomes
are influenced by the stage of the disease, the presence or lack of various factors
associated with higher-risk disease, the overall health of the patient and other
factors. Studies suggest that newer treatment combinations and approaches
may improve the length of survival. People with CLL should consult with their
physicians to discuss individual potential outcomes.
The National Cancer Institute-sponsored Working Group has recommended

criteria to describe responses to CLL therapy. A summary of this information is
presented in Table 4 on page 24; it may help people with CLL who want to discuss
the results of drug studies with their physicians and to make informed treatment
decisions.
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Table 4. Responses to CLL Therapy
Complete Response (CR)

• No evidence of clinical disease for at least two months after the
completion of treatment, including normal blood count (at least 1,500
neutrophils, 100,000 platelets, and <4,000 lymphocytes per microliter of
blood)
• Hemoglobin >11 g/dL without transfusions
• No CLL symptoms or enlarged lymph nodes or spleen
Partial Response (PR)

• At least a 50 percent reduction in the number of blood lymphocytes and
in lymph node and spleen enlargement
• One or more of the following must also be maintained for at least two
months: platelets greater than 100,000/μL; hemoglobin >11 g/dL; or a
50 percent improvement over pretreatment red cell or platelet counts
without transfusions
Nodular Partial Response

• Same as CR but with persistent lymphocytic nodules in the marrow
Progressive Disease
At least one of the following:
• Increase of at least 50 percent in absolute lymphocyte count or

transformation to higher-risk disease
• Increase of at least 50 percent in liver or spleen size or new appearance

of enlarged liver or spleen
• Increase of at least 50 percent in the sum of the products of at least two

lymph nodes on two consecutive exams performed two weeks apart
• New appearance of enlarged lymph nodes
Stable Disease
• Absence of CR or PR, without progressive disease
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Follow-up Care
People with CLL need regular medical follow-up after they have completed
treatment. It is important to assess the full effect of therapy as well as to identify
any return of progressive disease that may require additional therapy.
Minimal Residual Disease. Some people with CLL have such a low level of
remaining CLL cells after treatment that these cells cannot be detected by the
usual clinical tests, such as blood and marrow examinations. The term used for
this condition is “minimal residual disease” (MRD). More sensitive tests may be
performed to detect the presence of abnormal cells. The methods generally used to
detect MRD in people with CLL are four-color cell flow cytometry and polymerase
chain reaction (PCR). The benefit of PCR is associated with the test’s ability to
recognize a rearrangement in the DNA of the CLL cell. The rearrangement serves
as a marker that can be identified and measured by PCR. These techniques may
provide information that can help the physician to recognize a disease relapse and
to start treatment again.
People who have been treated for CLL and/or other cancers are encouraged to
keep a record of the treatments they have received. It is a good idea to share these
records with the physicians who monitor general health problems, both during
treatment and after treatment ends. Regular screening and monitoring for skin,
colorectal, breast and other types of cancer is advisable.
Related Diseases
The diseases mentioned in this section result from the cancerous transformation of
a type of lymphocyte; the accumulation of these cancer cells occurs mainly in the
marrow, the blood and the spleen (see Table 5 on page 26).
There are distinguishing characteristics that enable the hematology oncologist

to identify each disease, including the appearance and the immunophenotype
of the cancer cells; the cells’ varying effects on normal marrow and blood cell
development; and the cells’ varying effects on other parts of the body, such as the
kidneys, bowels and nervous system.
The diseases represent a range of clinical severity. At one end of the range, there are
the diseases that may be stable and may not advance in severity for some months or
years, or occasionally indefinitely. At the other end of the range, there are diseases
associated with difficulties that may be present at diagnosis and possibly get worse,
requiring immediate treatment and frequent observation.
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Table 5. CLL and Related Diseases
Less rapidly progressive
Chronic lymphocytic leukemia
Hairy cell leukemia
Large granular lymphocytic leukemia
Small cell lymphocytic lymphoma
Waldenström macroglobulinemia
More rapidly progressive
Prolymphocytic leukemia
Mantle cell lymphoma
Most rapidly progressive

Acute lymphocytic leukemia
T-Cell CLL. This is an uncommon disorder that is grouped with other T-cell
variants of leukemia or lymphoma, including T-cell prolymphocytic leukemia,
large granular lymphocytic leukemia and cutaneous T-cell lymphomas, such as
Sézary syndrome. People with T-cell CLL usually have a high white count and
an enlarged spleen. This disease may also affect the skin and lymph nodes. It can
be more rapidly progressive than B-cell CLL. However, some people do not have
progressive disease and may do well for long periods.
Some drugs that are often useful in B-cell CLL treatment, such as alkylating agents,
may be less effective in treating people with T-cell CLL. However, alemtuzumab
(Campath) attacks both T cells and B cells, and has shown promise in treating
T-cell CLL. The drugs cladribine and fludarabine may also have activity but are
less effective in treating people with T-cell CLL than B-cell CLL. In younger
people with T-cell CLL, high-dose chemotherapy followed by allogeneic stem cell
transplantation may be beneficial.
Cutaneous T-Cell Lymphoma. See the free LLS fact sheet Cutaneous T-Cell
Lymphoma for more information about this disease.
Prolymphocytic Leukemia. This disease can be a B-cell or a T-cell type and

features large numbers of lymphocytes in the blood. These lymphocytes
are a mixture of small lymphocytes akin to CLL cells and large, more
immature-appearing lymphocytes akin to acute lymphocytic leukemia cells.
In general, prolymphocytic leukemia develops more rapidly than the chronic
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form of lymphocytic leukemia, but more slowly than the acute form. It is
treated with the same drugs that are used for other types of lymphocytic
leukemia. In addition, there are a number of clinical trials to study new
treatment approaches for prolymphocytic leukemia.
Hairy Cell Leukemia. See the free LLS fact sheet Hairy Cell Leukemia for
more information about this disease.
Waldenström Macroglobulinemia. See the free LLS fact sheet Waldenström

Macroglobulinemia for more information about this disease.
Large Granular Lymphocytic (LGL) Leukemia. LGL leukemia is another

type of chronic leukemia of the lymphocytes. It is characterized by larger
lymphocytes containing noticeable granules, which can be seen when the
blood is examined under a microscope (see Figure 4, Panel C, on page 20).
These are not features of cells in other types of CLL. LGL leukemia is either
T-cell type or NK-cell type. The blood lymphocyte count is always elevated
in CLL. However, it is often normal or low in LGL leukemia. Although the
liver and spleen may be enlarged in LGL leukemia, the lymph nodes are not.
This is another feature that distinguishes it from CLL. For patients with T-cell
LGL leukemia, chemotherapy, if required, with low-dose methotrexate or
cyclophosphamide, or treatment with cyclosporine, an immunomodulatory
drug, may be helpful in improving the neutrophil count and the red cell
count. Granulocyte-colony stimulating factor (G-CSF) may also be part of
therapy to improve neutrophil counts, especially if an infection is present.
Alemtuzumab (Campath), which destroys large granular lymphocytes, is
being studied in clinical trials as a potential treatment. NK-cell LGL leukemia
is very resistant to therapy.
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Social and Emotional Effects
A CLL diagnosis may provoke a strong emotional response in patients, family
members and friends. No one response is either universal or unexpected. Most
people with CLL are able to cope with a diagnosis that at first may seem too hard
to accept. Acceptance usually takes time. It may help to know that progress has
been made in recent years and additional research is under way to identify new
targets and drugs for CLL.
People who are newly diagnosed with CLL may want to focus on learning about
their disease and its treatment. Patients and caregivers are encouraged to talk
with their doctor, to ask questions and to discuss their fears or concerns. A
second opinion from a specialist, such as a hematology oncologist, may also be
helpful. Healthcare professionals are available to spend time with patients, answer
questions, lend emotional support and provide referrals to other resources. Once
treatment begins, many people shift their focus to the prospect of recovery. Over
time, some patients say they tend to worry less about “the little things in life” and
place more importance on family, work and their relationships with other people.
People with CLL may want a friend, family member or caregiver to go with them
to treatments, especially the first several times. The company of another person
may help ease the stress. This person can also help the patient ask questions as
well as record and retain treatment information. While it is not always possible
to have this type of support, people with CLL can reach out in other ways—for
example, local or Internet support groups can provide a forum to discuss
healthcare appointments and other aspects of treatment. Over time, some people
with CLL form supportive relationships with members of their healthcare team.
Often, people with CLL meet other patients with cancer, and these friendships
provide support.
Both the course of the disease and how people react to living with CLL varies.
Even so, people with CLL have serious concerns. Some may be worried that their
diagnosis of CLL means that other family members may be at increased risk of
the disease, but typically this is not the case. However, if more than one family
member is diagnosed with CLL, genetic counseling may be helpful.
Lifestyle. A change in lifestyle occurs for many people with CLL, at least for a time.
Daily routines for people with CLL, and sometimes for their loved ones, may have to
be adjusted to accommodate treatment schedules. Disease and treatment side effects
may cause a person with CLL to question his or her self self-worth, identity and
appearance. These issues may affect relationships, including sexual relationships.
Sexual desire may decrease for a period of time, then return. Recognition that
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these feelings are normal and knowing that many side effects are temporary, and/
or can be treated effectively, may be reassuring. Open, honest communication in
relationships regarding fears and concerns can be very helpful for many people
with CLL.
Other lifestyle issues include diet, exercise and the use of tobacco products, such as
cigarette smoking or chewing tobacco. There is no firm evidence that a specific type
of diet or tobacco use increases the risk of CLL, and there is also no firm evidence
that a change in diet or cessation of tobacco use will have an impact on the course
of the disease. However, healthcare providers generally recommend that people
with cancer quit smoking or chewing tobacco and follow a healthful, balanced diet
that includes a variety of food groups.
People with CLL are also advised to stay physically active, as this can help
both emotional and physical health. However, people should consult with their
physicians to make sure that it is safe for them to exercise.
Finances. Treatment for CLL can be a financial strain for many individuals or their
families due to the loss of income and the high cost of medications and procedures.
LLS has the Patient Financial Aid Program, which offers a limited amount
of financial assistance for those in need who are under a physician’s care for a
confirmed blood cancer diagnosis. LLS also has the Co-Pay Assistance Program to
help patients with the cost of private health insurance premiums, private insurance
co-pay obligations, Medicare Part B, Medicare Plan D, Medicare Supplementary
Health Insurance and Medicare Advantage premium or co-pay obligations.
Public or private prescription drug coverage is required to qualify for the Co-Pay
Assistance Program, and financial assistance is based on medical and financial
eligibility and the availability of funds by disease diagnosis (see We Can Help on
page 30 for contact information).
Depression. It is important that an individual seek medical advice if his or her

mood does not improve over time. For example, if a person is feeling depressed
every day for a two-week period, he or she should contact a physician or another
member of the healthcare team. Depression is an illness that should be treated even
when a person is under medical care for CLL. Treatment for depression has proven
benefits for people living with cancer. There are many sources of help available to
people with cancer and their caregivers. Aspects of care, such as making treatment
choices, finding the time and money for medical care and communicating with
family members and friends can be stressful. Contact LLS or ask your healthcare
team for guidance and referrals to other sources of help, such as support groups,
counseling services or community programs. The National Institute of Mental
Health (NIMH) has several publications about depression that may be helpful.
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For more information, go to www.nimh.nih.gov and enter “depression” in the search
box at the top of the Web page, or call NIMH at (866) 615-6464.
We Can Help
LLS offers support programs through its national office and local chapters to help
ease the emotional stresses that come with a blood cancer diagnosis.
Visit www.LLS.org or contact the Information Resource Center at (800) 955-4572
to locate a chapter in your area, order free publications or speak to an Information
Specialist. For more support information, see the free LLS booklets Each New Day:
Ideas for Coping with Blood Cancers and Service & Support.
Language Services. Members of your healthcare team want you to understand the
information they are giving you. Let your physician know if you want a professional
healthcare interpreter who speaks your native language or uses sign language. Many
times, this is a free service. Contact a patient advocate if you are not sure. For more
information, contact the Information Resource Center (IRC) at (800) 955-4572.
Language services are available for IRC calls.
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Glossary
Alkylating Agent
A type of chemotherapy used to kill cancer cells by interfering with cancer cell
division. Alkylating agents cause side effects because they also interfere with
cell division in certain healthy tissues where cell division is frequent, such as the
gastrointestinal tract. Cyclophosphamide is one of several types of alkylating agents.
Allogeneic Stem Cell Transplantation

A treatment that uses donor stem cells to restore a patient’s marrow and blood
cells. First, the patient is given “conditioning therapy” (high-dose chemotherapy
or high-dose chemotherapy with total body radiation) to treat the leukemia and
to “turn off” the patient’s immune system so that the donor stem cells will not be
rejected. A type of transplant called a “nonmyeloablative” or “reduced-intensity”
transplant is under study in clinical trials. It uses lower doses of conditioning
therapy and may be safer, especially for older patients. (For more information, see
the free LLS booklet Blood and Marrow Stem Cell Transplantation).
Anemia
A decrease in the number of red cells and, therefore, the hemoglobin concentration
in the blood. The blood is less able to carry oxygen as a result. If severe, anemia can
cause a pale complexion, weakness, fatigue and shortness of breath.
Antibodies
Proteins released by plasma cells that recognize and bind to specific foreign
substances called “antigens.” Antibodies coat, mark for destruction or inactivate
foreign particles, such as bacteria, and viruses or harmful toxins. Antibodies can
also be made in the laboratory, in two ways. The first way takes advantage of the
fact that if material is injected from one species into a different species, the latter
will recognize it as foreign and make antibodies to it. These antibodies are usually
polyclonal antibodies; that is, they react to multiple targets (antigens). The second
way involves monoclonal antibodies, which react to only one target (antigen) and
can be used in several important ways. They can be used to identify and classify
types of blood cancers or be altered so as to become useful in antibody-mediated
immunotherapy.
Apheresis
The process of removing the needed components of a donor’s blood and returning
the unneeded parts to the donor. The process, also called “hemapheresis,”
circulates blood from a donor through a filter-type apparatus, and then back to the
donor. Apheresis makes it possible to remove desired elements from large volumes
of blood. Platelets, red cells, white cells and plasma can be removed separately.
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For example, this technique permits the harvest of enough platelets for transfusion
from one donor (rather than six to eight separate donors). In this way, the recipient
of the platelets is exposed to fewer donors or can be given HLA-matched platelets
from a single related donor. This technique is also used to remove circulating blood
stem cells, which can be frozen and stored for later use in transplant.
Autologous Stem Cell Transplantation

A technique used to delay the progression of certain blood cancers. The autologous
transplantation process takes place after the patient achieves a complete response
(remission), or a good partial response, to induction drug therapy. The process is as
follows: 1) the patient’s stem cells are harvested, usually from the blood; 2) the stem
cells are frozen for later use and the patient receives conditioning drug therapy; 3)
the stem cells are thawed and infused back to the patient through an indwelling
catheter (central line). The main adverse side effects of the transplant are the results
of the conditioning therapy; these include mouth sores, hair loss, nausea, vomiting,
diarrhea and risk of infections. Patients receive supportive care to help prevent
and/or manage the side effects. Generally, after 10 to 14 days, blood counts begin
to normalize and the side effects of the conditioning therapy begin to resolve.
Banding of Chromosomes
The staining of chromosomes with dyes that highlight transverse bands or regions on
the chromosome. The bands give the chromosomes more specific features, allowing
individual distinctions to be made among them. This technique permits more precise
identification of chromosomes. See Fluorescence In Situ Hybridization.
Basophil
A type of white cell that participates in certain allergic reactions.
Beta 2-Microglobulin (B2M)

A protein that is shed from CLL cells. The degree of elevation of serum B2M
appears to correlate with IgHv mutation status and ZAP-70. A patient with a high
ZAP-70 or an unmutated IgHv gene status is more likely to have a high B2M level.
This test to measure B2M is available in most laboratories in the United States.
Blast Cells
The earliest marrow cells identified by the light microscope. Blasts represent up
to 5 percent of normally developing marrow cells. They are largely myeloblasts,
which are cells that will develop into neutrophils. In normal lymph nodes, blasts
are usually lymphoblasts; that is, cells that are part of lymphocyte development.
In forms of acute leukemia, blast cells similar in appearance to normal blast cells
accumulate in large numbers, perhaps up to 80 percent of all marrow cells. In acute
myelogenous leukemia, myeloblasts accumulate. In acute lymphocytic leukemia,
lymphoblasts accumulate. The distinction sometimes can be made by examination
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of stained marrow cells through the microscope. Often, immunophenotyping or
the use of specially stained marrow cells is required to be sure of the difference.
Bone Marrow
A spongy tissue that is the site of blood cell formation in the central cavity of the
bones. By puberty, the marrow in the spine, ribs, breastbone, hips, shoulders and
skull is most active in blood cell formation. In adults, the bones of the hands,
feet, legs and arms do not contain marrow in which blood cells are made. In these
sites, the marrow is filled with fat cells. When marrow cells have matured into
blood cells, they enter the blood that passes through the marrow and are carried
throughout the body.
Bone Marrow Aspiration

A test to examine marrow cells to detect abnormalities. A marrow sample is usually
taken from the patient’s hip bone. After medication is given to numb the skin, the
liquid sample is removed using a special needle inserted through the bone into
the bone marrow. The sample is looked at under a microscope to detect abnormal
cells. The cells obtained can also be used for cytogenetic analysis and other tests.
Bone Marrow Biopsy

A test to examine marrow cells to detect abnormalities. This test differs from a
bone marrow aspiration in that a small amount of bone filled with marrow is
removed, usually from the hip bone. After medication is given to numb the area,
a special biopsy needle is used to remove a core of bone containing marrow. The
bone marrow is examined under a microscope to determine if abnormal cells are
present. Bone marrow aspiration and biopsy may be done in the physician’s office
or in a hospital. The two tests are almost always done together. Both tests are also
done after treatment to determine the proportion of blood cancer cells that have
been killed by therapy.
Bone Marrow Transplantation See Allogeneic Stem Cell Transplantation and

Autologous Stem Cell Transplantation.
CD38
An antigen on CLL cells and other cells. The expression of CD38 may be a marker
to assist in predicting CLL progression.
Central Line
A special tube inserted into a large vein in the upper chest. The central line,
sometimes referred to as an “indwelling catheter,” is tunneled under the skin of
the chest to keep it firmly in place. The external end of the catheter can be used to
administer medications, fluids or blood products or to withdraw blood samples.
With meticulous care, central lines can remain in place for long periods
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of time (many months) if necessary. They can be capped and remain in place in
patients after they leave the hospital, and be used for outpatient chemotherapy
or blood product administration. Several types of catheters (for example,
Groshong®, Hickman®, and Broviac®) can be used for patients receiving intensive
chemotherapy or nutritional support.
Chemotherapy
The use of chemicals (drugs or medications) to kill cancer cells. Many chemicals
have been developed for this purpose; most act to injure the DNA of the cancer
cells in such a way that the cancer cells cannot grow or survive. Successful
chemotherapy depends on the fact that cancer cells are somewhat more sensitive
to chemotherapy than normal cells. However, the cells of the marrow, the
gastrointestinal tract, the skin and the hair follicles are also especially sensitive
to chemotherapy; this causes the common side effects of chemotherapy, such as
nausea, mouth sores and hair loss.
Chromosome
Any of the 46 structures in the nucleus of all cells in the human body (except the
red cells) that contain a strand of DNA. This strand is made up principally of genes,
which are specific stretches of the DNA. “Genome” is the term for an organism’s
complete set of DNA. The human genome has been estimated to contain about
30,000 genes. The genes on the X and Y chromosomes are the determinants of
our gender: two X chromosomes produce a female and an X and a Y chromosome
produce a male. Each chromosome has a long arm (called “q”) and a short arm
(called “p”). The number or size of chromosomes may be altered in blood cancer
cells as a result of chromosome breakage and rearrangement (translocation).
Clonal
The designation for a population of cells derived from a single transformed parent
cell. Virtually all cancers are derived from a single cell with an injury to its DNA
(mutation) and thus are monoclonal. Leukemia, lymphoma, and myeloma are
examples of clonal cancers; that is, cancers derived from a single abnormal cell.
Cluster Designation (CD)

A term used with a number to identify a specific molecule on the surface of an
immune cell. It is commonly used in its abbreviated form, for example, “CD20”
(the target of the monoclonal antibody therapy rituximab) and “CD52” (the target
of the monoclonal antibody therapy alemtuzumab).
Colony-Stimulating Factor See Growth Factors.
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Cytogenetic Analysis
The process of analyzing the number and size of the chromosomes of cells. In
addition to detecting chromosome alterations, in some cases it is possible to
identify the actual genes that have been affected. These findings are very helpful in
diagnosing specific types of blood cancers, in determining treatment approaches
and in following the response to treatment. The individual who prepares and
examines the chromosomes and interprets the results is called a “cytogeneticist.”
Differentiation
The process by which stem cells give rise to functional cells of a single blood
cell line. Differentiation of stem cells forms red cells, platelets and white cells
(neutrophils, monocytes, eosinophils, basophils and lymphocytes).
Eosinophil
A type of white cell that participates in allergic reactions and helps fight certain
parasitic infections.
Erythrocytes See Red Cells.
Flow Cytometry
A test that permits the identification of specific cell types within a sample of cells.
The test may be used to examine blood cells, marrow cells or cells from a biopsy.
A diluted suspension of cells from one of these sources can be tagged with an
antibody specific for a site on the cell surface. The antibody has a chemical
attached that will emit light when activated by a laser beam. The cells flow
through the instrument called a “flow cytometer”; when the cells pass through its
laser beam, those with the antibody-specific surface feature light up and then can
be counted.
One use of flow cytometry is to determine whether a sample of cells is composed

of T cells or B cells. This permits the physician to determine if the leukemia or
lymphoma is of the B- or T-cell type. Flow cytometry is also used to select stem
cells from a mixed-cell population so that they can be used later in a stem cell
transplant.
Fluorescence In Situ Hybridization (FISH)

A technique that can be used to see if cytogenetic abnormalities characteristic
of CLL or other blood cancers are in the nucleus of the person’s cancer cells.
FISH uses DNA-binding agents that are specific for the pieces of DNA (parts of
chromosomes) of interest. FISH can be helpful in assessing risk and treatment
needs, and for monitoring treatment effectiveness, by providing a sensitive test to
see abnormal cells, such as cells with deletions of 17p.
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G-Banding Karyotyping
A “karyotype” is the systematic arrangement, using images, of the 46 human
chromosomes of a cell. Karyotypes are examined for deviations from the expected
arrangement, number, size, shape or other characteristics of the chromosomes.
Each chromosome pair has a characteristic banding pattern. To make the
banding pattern easier to see, a dye called Giemsa may be used as a stain. This
is also referred to as “G-banding.” G-banding karyotyping and other cytogenetic
tests provide physicians with information that contributes to determining the
best treatment approach for each individual. G-banding karyotyping and other
cytogenetic tests can take several weeks after cells are obtained from a bone
marrow aspiration, since they have to be grown in a laboratory and then stained
and examined individually. Thus, these tests take longer than the FISH test, but
because these tests do not rely on specific probes for any particular chromosome,
they have the advantage of allowing the examiner to detect changes that are visible
in any chromosome.
Graft-Versus-Host Disease (GVHD)

The immune attack by lymphocytes in a donor’s marrow or blood cell suspension
(the graft) against the tissues of the recipient (the host). The immune cells most
engaged in this reaction are donor T lymphocytes, which are present in the donor’s
blood or marrow, the source of stem cells. The principal sites of attack are the
skin, the liver and the gastrointestinal tract. The reaction does not occur in
identical-twin transplants. The reaction may be minimal in closely matched
individuals or severe in less well-matched individuals. These reactions are
mediated in part by antigens that are not in the major HLA system and cannot
be matched prior to transplantation. For example, in the case of a female stem
cell donor and a male recipient, factors that are produced by genes on the Y
chromosome may be seen as foreign by the female donor’s cells, which do not
share the genes on the Y chromosome. This fact does not prohibit female donors
and male recipients, but it makes the risk of immune reaction higher.
Graft-Versus-Tumor Effect (Graft-Versus-Leukemia Effect)

The potential immune reaction of transplanted (donor) T lymphocytes to recognize
and attack the malignant cells of the recipient. This effect was noted when 1)
disease recurrence after transplant was seen to be more likely if the donor and
recipient were identical twins than if they were nonidentical siblings; 2) disease
recurrence was less likely the more pronounced the graft-versus-host disease
was; and 3) the removal of donor T lymphocytes decreased the incidence of graft-
versus-host disease but also resulted in a higher frequency of disease relapse.
Each of these observations could be explained best as an immune attack by donor
lymphocytes against recipient tumor cells that, along with the intensive
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conditioning treatment, serve to keep the disease in check. This effect seems to be
most active in types of myeloid leukemia, although it may also occur in patients
with other blood cancers.
Granulocyte
A type of white cell that has a large number of granules in the cell body.
Neutrophils, eosinophils and basophils are types of granulocytes.
Growth Factors
Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony
stimulating factor (GM-CSF) are examples of growth factors that are made
commercially. They are used to stimulate the production of neutrophils and shorten
the period of low neutrophil counts in the blood after chemotherapy.
GM-CSF can also stimulate monocytes.
Hemapheresis See Apheresis.
Hematologist
A physician who specializes in the treatment of blood cell diseases. This person is
either an internist who treats adults or a pediatrician who treats children.
Hematopathologist
A type of pathologist who studies diseases of blood cells by looking at peripheral
blood smears, bone marrow aspirates and biopsies, and lymph nodes and other
tissue, and uses his or her expertise to identify blood cancers and other diseases. In
addition to using a microscope, a hematopathologist also uses laboratory values,
flow cytometry and molecular diagnostic tests to make the most accurate diagnosis.
The hematopathologist works closely with the hematologist.
Hematopoiesis
The process of blood cell development in the marrow. The most undeveloped cells
in the marrow are stem cells. They start the process of blood cell development. The
stem cells begin to develop into young or immature blood cells, such as red cells
or various types of white cells. This process is called “differentiation.” The young
or immature blood cells then further develop into fully functional blood cells. This
process is called “maturation.” Mature cells leave the marrow and enter the blood
and circulate throughout the body. Hematopoiesis is a continuous process that is
active normally throughout life. The reason for this constant activity is that most
blood cells live for short periods and must be replaced continuously. After release
from the marrow, red cells are removed in four months, platelets in 10 days, and
most neutrophils in one to three days. About 500 billion blood cells are made each
day. This requirement for very rapid replacement explains the severe deficiency
in blood cell counts that occurs when the marrow is injured by the leukemia,
lymphoma or myeloma disease process.
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HLA
The acronym for “human leukocyte antigen(s).” These are proteins on the surface
of most tissue cells, and they give an individual his or her unique tissue type. HLA
factors are inherited from mother and father, and the greatest chance of having the
same HLA type is between siblings. On average, one in four siblings is expected
to share the same HLA type. The testing for HLA antigens is referred to as “tissue
typing.” There are six major groups of HLA antigens: A, B, C, D, Dr, and Dq. The
proteins on the surface of cells act as antigens when donated (transplanted) to
another individual, the recipient. If the antigens on the donor cells are identical
(for example, in identical twins) or very similar (for example, in HLA-matched
siblings), the transplant (donated stem cells) is more likely to survive (engraft) in
the recipient. In addition, the recipient’s body cells are less likely to be attacked by
the donated immune cells (a result called “graft-versus-host disease”).
Immunoconjugate (Therapeutic Immunoconjugate)

A monoclonal antibody fused to potent toxins or cytotoxic agents.
Immunoglobulin Heavy Chain Variable Region (IgHv) Gene Status

A marker that can distinguish between CLL subtypes (unmutated IgHv and
mutated IgHv). People with CLL with unmutated IgHv gene status may have a
more progressive form of the disease.
Immunophenotyping
A method that uses the reaction of antibodies with cell antigens to determine a
specific type of cell in a sample of blood cells, marrow cells or lymph node cells.
The antibodies react with specific antigens on the cell. A tag is attached to an
antibody so that it can be detected. The tag can be identified by the laboratory
equipment used for the test. As cells carrying their array of antigens are tagged
with specific antibodies, they can be identified.
Indwelling Catheter See Central Line.
Karyotype
The systematic arrangement, using images, of the 46 human chromosomes of a cell in
22 matched pairs (maternal and paternal member of each pair) by length from longest
to shortest and other features. These 22 pairs are referred to as “autosomes.” The sex
chromosomes are shown as a separate pair (either XX or XY).
Leukocytes See White Cells.
Leukopenia
A decrease below normal in the number of blood leukocytes (white cells).
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Lymphadenopathy
Enlargement of lymph nodes.
Lymphatic System
The system comprising the lymph nodes, the thymus gland (in the first several
decades of life), the lymphatic channels and the lymphatic tissue of the marrow,
the gastrointestinal tract, the skin and the spleen, and including the T, B and NK
lymphocytes contained in those sites.
Lymph Nodes
Small bean-sized structures that contain large numbers of lymphocytes and are
connected with each other by small channels called “lymphatic vessels.” These nodes
are distributed throughout the body. In patients with lymphoma and some types of
lymphocytic leukemia, the malignant lymphocytes grow and expand the lymph nodes
so that they may become enlarged. This enlargement of lymph nodes can be seen,
felt or measured by computed tomography (CT) scan or magnetic resonance imaging
(MRI), depending on the degree of enlargement and location.
Lymphocyte
A type of white cell that is the essential cell type in the body’s immune system.
There are three major types of lymphocytes: B lymphocytes, which produce
antibodies to help combat infectious agents such as bacteria, viruses and fungi; T
lymphocytes, which have several functions, including assisting B lymphocytes in
making antibodies; and natural killer (NK) cells, which can attack virus-infected
cells or tumor cells.
Macrophage See Monocyte.
Minimal Residual Disease (MRD)

The term used to describe the small amounts of cancer cells that may remain after
treatment, even when blood and marrow may appear to be normal. These residual
cells can only be identified by sensitive molecular techniques.
Monoclonal See Clonal.
Monoclonal Antibodies
Antibodies made by cells belonging to a single clone. These highly specific antibodies
can be produced in the laboratory. They are very important reagents for identifying
and classifying disease by the immunophenotyping of cells. They also have clinical
applications for targeted delivery of drugs to cancer cells, and can be used to purify
cells used for stem cell transplants.
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Monocyte (Macrophage)
A type of white cell that represents about 5 to 10 percent of the cells in normal
human blood. The monocyte and the neutrophil are the two major microbe-
eating cells in the blood. When monocytes leave the blood and enter the tissue,
they are converted to macrophages. The macrophage is the monocyte in action: it
can combat infection in the tissue, ingest dead cells (in this function it is called a
“scavenger cell”) and assist lymphocytes in their immune functions.
Multidrug Resistance (MDR)

A characteristic of cells that makes them resistant to the effects of several different
classes of drugs. There are several forms of drug resistance. They are each
determined by genes that govern how the cell will respond to the chemical agents.
One type of multidrug resistance involves the ability to force several drugs out of
cells. The outer wall of the cell contains a pump that ejects chemicals, preventing
them from reaching a toxic concentration. The resistance to drugs can be traced
to the expression of genes that direct the formation of high amounts of a protein
that prevents the drugs from having their effects on the malignant cells. If the gene
or genes involved are not expressed or are weakly expressed, the cells are more
sensitive to the drug’s effect. If the genes are highly expressed, the cells are less
sensitive to the drug’s effect.
Mutation
An alteration in a gene that results from a change to a part of DNA. A “germ cell
mutation” is present in the egg or the sperm and can be transmitted from parent(s)
to children. A “somatic cell mutation” occurs in a specific tissue cell and can result
in the growth of that specific tissue cell into a tumor. Most cancers start after a
somatic mutation. Leukemia, lymphoma and myeloma are caused by a somatic
mutation in a primitive marrow (blood-forming) or lymphatic system cell.
Myelocyte
A cell of the marrow that is a precursor of the mature granulocytes of the blood.
Myelocytes are not present in the blood of healthy individuals.
Neutropenia
A below-normal concentration of neutrophils, a type of white cell.
Neutrophil
A type of white cell that combats infections. Patients with certain blood cancers
or patients who have undergone chemotherapy often do not have sufficient
quantities of neutrophils circulating in their bloodstream. A severe deficiency of
neutrophils increases the patient’s susceptibility to infection.
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Nonmyeloablative Allogeneic Stem Cell Transplantation See Reduced-Intensity
Stem Cell Transplantation.
Oncologist
A physician who diagnoses and treats patients with cancer. Oncologists are usually
internists who treat adults or pediatricians who treat children. Radiation oncologists
specialize in the use of radiation to treat cancer. Surgical oncologists specialize in the
use of surgical procedures to diagnose and treat cancer. These physicians cooperate
and collaborate to provide the best treatment plan for the patient.
Pancytopenia
A below-normal concentration of all three of the major blood cell types: red cells,
white cells and platelets.
Petechiae
Pinhead-sized sites of bleeding in the skin. This type of bleeding results from a very
low platelet count. The small hemorrhages are frequently seen on the legs, feet,
trunk and arms. They change in color from red to brown, and eventually disappear.
They stop developing when the platelet count increases.
Phagocytes
Cells that readily eat (ingest) bacteria, fungi, and other microorganisms to protect
the body against infection. The two principal phagocytes are neutrophils and
monocytes. They leave the blood and enter tissue in which an infection has
developed. A severe decrease in the concentrations of these cells is the principal
cause of susceptibility to infection in patients treated with intensive radiation
therapy and/or chemotherapy. Treatment may suppress blood cell production in the
marrow, resulting in deficiencies of these phagocytic cells.
Platelets
Blood cells that stick to the site of blood vessel injury and seal off the injured blood
vessel to stop bleeding. “Thrombocyte” is another word for platelet and is often
used in describing disorders of platelets, such as thrombocytopenia (too few) or
thrombocythemia (too many).
Platelet Transfusion
The transfusion of donor platelets that may be needed to support some people
receiving treatments for CLL and other blood cancers. Platelets can be gathered
from several unrelated donors and given as pooled, random-donor platelets.
Platelets from approximately six single-unit blood donors are required to
significantly raise the platelet count in a recipient. Sufficient platelets can be
obtained from one donor by a procedure known as “apheresis.” This technique
skims the platelets from large volumes of blood as it passes through the apheresis
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machine. The red cells and plasma are returned to the donor. The advantage of
a transfusion of single-donor platelets is that the patient is not exposed to the
different antigens on platelets from many different people, and thus is less likely
to develop antibodies against donor platelets. HLA-matched platelet transfusion
can be given from a related or an unrelated donor who has an identical HLA
tissue type or very similar HLA tissue type.
Polymerase Chain Reaction (PCR)

A technique to expand trace amounts of DNA or RNA so that the specific type of
the DNA or RNA can be studied or determined. This technique has become useful
in detecting a very low concentration of residual blood cancer cells, too few to be
seen using a microscope. PCR can detect the presence of one blood cancer cell
among 500,000 to one million blood cancer cells. PCR requires a specific DNA
(or RNA) abnormality or marker, like an oncogene, in cancer cells to be used for
identifying residual abnormal cells.
Promyelocyte
A cell that is formed in the transition from an immature cell to a mature cell during
the development cycle for certain types of white cells.
Red Cells
Red cells (erythrocytes) carry hemoglobin, which binds oxygen and carries it to the
tissues of the body. Red cells make up about 40 to 45 percent of the volume of the
blood in healthy individuals.
Reduced-Intensity Stem Cell Transplantation

A form of allogeneic transplantation now in clinical trials. In a reduced-
intensity transplant, patients receive lower doses of chemotherapy drugs and/
or radiation in preparation for the transplant. Immunosuppressive drugs
are used to prevent rejection of the graft, and the engraftment of donor
immune cells may allow these cells to attack the disease (graft-versus-tumor
effect). Studies to determine the usefulness of reduced-intensity stem cell
transplantation in older patients are also under way. (For more information
about all types of stem cell transplantation, see the free LLS booklet Blood
and Marrow Stem Cell Transplantation.)
Refractory CLL
The term used to describe CLL that does not result in a remission (but may be
stable) or disease that gets worse within six months of the last treatment.
Relapsed CLL
The term for CLL that responded to therapy but, after six or more months,
stopped responding.
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Remission
The disappearance of evidence of a disease, usually as a result of treatment. The
words “complete” and “partial” are sometimes used to further define “remission.”
Complete remission means that all evidence of the disease is gone. Partial
remission means that the disease is markedly improved by treatment, but residual
evidence of the disease is present.
Resistance to Treatment
The ability of cells to grow despite exposure to a chemical that ordinarily kills cells
or inhibits their growth. Refractory disease is the condition in which a proportion
of malignant cells resist the damaging effects of a drug or drugs. Cells develop drug
resistance in several different ways. (See Multidrug Resistance.)
Richter Transformation
In a small proportion of patients, a progression in their CLL in which their disease
becomes more characteristic of an aggressive lymphoma. This change is not a second
cancer, but a transformation of the CLL cells.
Spleen
An organ located in the left upper portion of the abdomen just under the left side
of the diaphragm. It contains clusters of lymphocytes and also filters old or worn-
out cells from the blood. It is often affected in CLL and lymphoma. Enlargement
of the spleen is called “splenomegaly.” Surgical removal of the spleen is known
as “splenectomy.” Certain diseases are treated by removing the spleen. Most of
the functions of the spleen can be performed by other organs, such as the lymph
nodes and liver, but a person whose spleen has been removed is at higher risk
for infection. He or she is given antibiotic therapy immediately at the first sign of
infection, such as a fever.
Stem Cells
Primitive cells in the marrow that develop into red cells, white cells and
platelets. Stem cells are largely found in the marrow, but some leave the
marrow and circulate in the blood. Using special techniques, the stem cells in
the blood can be collected, preserved by freezing and later thawed and used
for stem cell therapy. (See Hematopoiesis.)
Stem Cell Transplantation See Allogeneic Stem Cell Transplantation and

Autologous Stem Cell Transplantation.
Thrombocytopenia
A below-normal concentration of platelets in the blood.
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Translocation
An abnormality of chromosomes in the marrow or lymph node cells that occurs
when a piece of one chromosome breaks off and sticks to the end of another
chromosome. In a balanced translocation, genetic material is exchanged between
two different chromosomes with no gain or loss of genetic information.
When a translocation occurs, the gene at which the break occurs is altered. This
is one form of somatic mutation that may transform the gene into an oncogene
(cancer-causing gene). (See Mutation.)
White Cells
The five major types of white cells: neutrophils, eosinophils, basophils, monocytes
and lymphocytes. White cells are also called “leukocytes.” See Normal Blood and
Marrow, pages 3-5.
ZAP-70
An abbreviation for the cell protein “zeta-associated protein 70.” A high level of
ZAP-70 expression on the cells of patients with B-cell CLL is one of several factors
that may predict more progressive disease.
Resources
Free LLS booklets, fact sheets and brochures include
Blood Transfusion
Choosing a Blood Cancer Specialist or Treatment Center
The CLL Guide—Information for Patients and Caregivers
Fatigue
Understanding Clinical Trials for Blood Cancers
Understanding Drug Therapy and Managing Side Effects
Understanding Lab and Imaging Tests
LLS sponsors conferences and meetings each year for researchers and healthcare
professionals and a range of teleconferences and Web casts on topics of interest to
patients and caregivers. Live and archived versions of these events are provided free
to the public. You can also watch the interactive LLS Web programs My Clinical
Trials Journey and My Personal CLL Journey. For more information, go to
www.LLS.org and click on “National Education Programs” or call (800) 955-4572.
Page 44
Other Web site features include the blood cancer discussion boards, an online
source of support among people living with CLL, and the “Select Reading List” of
suggested books on a wide range of subjects. LLS eNewsletters, news feeds and
podcasts offer up-to-date information on clinical trials, research and medical news.
Visit www.LLS.org to subscribe.
References
Foon KA, Boyiadzis M, Land SR, et al. Chemoimmunotherapy with low-dose
fludarabine and cyclophosphamide and high dose rituximab in previously untreated
patients with chronic lymphocytic leukemia. The Journal of Clinical Oncology.
2009;27(4):498–503. Epub 2008 Dec 15.
Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment
of chronic lymphocytic leukemia: a report from the International Workshop on
Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working
Group 1996 guidelines. Blood. 2008;111(12):5446-5456. Epub 2008 Jan 23.
Horner MJ, Ries LAG, Krapcho M, Neyman N, Aminou R, Howlader N, Altekruse

SF, Feuer EJ, Huang L, Mariotto A, Miller BA, Lewis DR, Eisner MP, Stinchcomb
DG, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2006, National Cancer
Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2006/, based on November
2008 SEER data submission, posted to the SEER Web site, 2009.
Kipps TJ. Chronic lymphocytic leukemia and related diseases. In: Lichtman MA,
Beutler E, Kipps TJ, Seligsohn U, Kaushansky K, Prcha JT, eds. Williams Hematology.
7th ed. New York, NY: McGraw-Hill; 2006:1343-1383.
Acknowledgement
LLS gratefully acknowledges for her critical review and important contributions to the
material presented in this publication:
Susan O’Brien, MD
Professor of Medicine and Medical Oncologist
Department of Leukemia
The University of Texas M.D. Anderson Cancer Center
Houston, Texas
Page 45
For more information, please contact:
or:
Home Office
1311 Mamaroneck Avenue
White Plains, NY 10605
Information Resource Center (IRC) 800.955.4572 (Language interpreters available upon request.)
www.LLS.org
Our Mission: Cure leukemia, lymphoma,
Hodgkin’s disease and myeloma, and improve the
quality of life of patients and their families.
LLS is a nonprofit organization that relies on the generosity of corporate,

individual and foundation contributions to advance its mission.
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Chronic Lymphocytic

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Printing of this publication made

The Leukemia & Lymphoma Society (LLS) is committed to bringing you

LLS is the world’s largest voluntary health organization dedicated to

We wish you well.

Normal Blood and Marrow 3

The Lymphatic System 6

Chronic Lymphocytic Leukemia 7

Symptoms and Signs 9

Complications: CLL or CLL Treatment 19

Treatment Response and Follow-up 23

Social and Emotional Effects 28

LEUKEMIA LYMPHOMA MYELOMA

We’d Like to Hear From You

This publication is designed to provide accurate and authoritative information

Normal Blood and Marrow

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Differentiate & Differentiate &

Red Cells Basophils T Lymphocytes

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The three main types of lymphocytes are

• B lymphocytes (B cells), which make antibodies in response to invading bacteria,

• T lymphocytes (T cells), which have several functions, including helping B

Leukemia is called “lymphocytic” (or “lymphoblastic”) if the cancerous change

Chronic leukemia is a slow-growing blood cancer that permits the growth of

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Lymphocytic Leukemia and Lymphoma. The World Health Organization (WHO)

Acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL)

Chronic Lymphocytic Leukemia

People with faster-growing CLL may have

Symptoms and Signs

Bone Marrow Examination. A bone marrow aspiration and biopsy generally

Immunophenotyping. “Immunophenotyping” of lymphocytes is an important

Immunophenotyping is done with an instrument called a “flow cytometer.” A

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Immunoglobulin Levels. The measurement of the concentration of

• The elevation of blood and marrow leukemic lymphocyte counts

Table 1. Commonly Used CLL Staging Systems

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Trisomy 12 About 10 to 20 percent of patients have CLL cells with

Del 11q Up to 20 percent of people with CLL have deletions in

Chromosome 14 Structural abnormalities of chromosome 14 or chromosome 6

Blood lymphocyte doubling People with CLL whose lymphocyte number

B2M A higher level of serum beta 2-microglobulin,

CD38 CD is an abbreviation for “cluster designation,”

Unmutated IgHv The unmutated immunoglobulin heavy chain

ZAP-70 ZAP-70 (zeta-associated protein 70), when

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• Watch and wait

The goals of CLL treatments are to

• Slow the growth of the CLL cells

A person with CLL is usually treated by a hematologist or an oncologist. People

Table 2. Some Factors That Influence

*Several of these factors are often present at the same time.

Chemotherapy. Fludarabine (Fludara®) is considered to be one of the most effective

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Monoclonal Antibody Therapy. Monoclonal antibodies are proteins that are

The monoclonal antibody therapies rituximab (Rituxan) and alemtuzumab

These therapies continue to be studied in clinical trials. Other new monoclonal

Radiation Therapy. Radiation is sometimes used to shrink large lymph node

Chemotherapy Monoclonal Antibody Therapy

• B lymphocytes (B cells), which make antibodies in response to invading bacteria,

• T lymphocytes (T cells), which have several functions, including helping B

• Granulocyte-colony stimulating factor (G-CSF) [filgrastim (Neupogen®) or

• Granulocyte-macrophage colony-stimulating growth factor (GM-CSF)

• Increase of at least 50 percent in absolute lymphocyte count or

• Increase of at least 50 percent in liver or spleen size or new appearance

• Increase of at least 50 percent in the sum of the products of at least two