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Chronic Lymphocytic Leukemia

About leukemia
Leukemia is a cancer of the blood. Leukemia begins when
normal blood cells change and grow uncontrollably. Chronic
lymphocytic leukemia (CLL) is a cancer of the lymphocytes, a
type of white blood cell involved in the bodys immune system.
In some people with CLL, the disease grows and progresses
slowly, and it may take years for symptoms to appear or for
treatment to be needed. In fact, some patients may never need
treatment for their CLL. In other patients the disease grows
more quickly and needs treatment sooner.
About lymphocytes
Lymphocytes circulate in the bloodstream and are made in the
lymph nodes, spleen, thymus, and bone marrow. Bone marrow
is the spongy, red tissue in the inner part of the large and flat
bones. There are three different types of lymphocytes: T cells,
B cells, and natural killer (NK) cells. Generally, T cells fight
infections by triggering other cells in the immune system and
by destroying infected cells, B cells make antibodies, and NK
cells fight microbes and cancer cells.

About CLL

In people with CLL, the abnormal cells crowd other types of cells in the bone marrow,
preventing the production of red blood cells that carry oxygen, other types of normal
white blood cells, such as neutrophils or granulocytes that fight infection, and platelets
that are needed for clotting. This means that people with CLL may have anemia from
low levels of red blood cells, are more likely to get infections because they do not have
enough white blood cells, and bruise or bleed easily because of a low level of platelets.
There are two general types of CLL, and it is important for doctors to find out whether
the disease is caused by the overgrowth of T cells or B cells. The T-cell type of CLL is
now called T-cell prolymphocytic leukemia and much less common than the B-cell type
of the disease. About 1% of people with CLL have the T-cell type. More than 95% of
people with CLL have the B-cell type.
Most often, CLL is diagnosed when too many abnormal lymphocytes are found in the
blood, also known as lymphocytosis. However, the same disease can occur when the
abnormal lymphocytes are mostly in the lymph nodes but not in the blood. This is called
small lymphocytic lymphoma, but it behaves very similarly to CLL.
Leukemia - Chronic Lymphocytic - CLL - Statistics
This year, an estimated 15,720 people of all ages (9,100 men and 6,620 women) in the
United States will be diagnosed with CLL. Children are almost never diagnosed with
CLL, but it is the most common type of leukemia diagnosed in adults. It is estimated
that 4,600 deaths (2,800 men and 1,800 women) from CLL will occur this year.
The survival rate for people with CLL varies widely according to the stage of the
disease and can range from about one year to more than 20 to 30 years. The five-year
survival rate is the percentage of people who survive at least five years after the cancer
is detected, excluding those who die from other diseases. The five-year survival rate of
people with CLL is about 79%.

Leukemia - Chronic Lymphocytic - CLL - Risk Factors


Family history. Although it is uncommon, more than one close relative may develop CLL or
some other lymph-related cancer. People with a first-degree relative with CLL, such as a
parent, sibling, or child, are two to four times more likely to develop the disease.
Age. CLL is most common in older adults, is rare in young adults, and hardly ever develops
in children. About 90% of people diagnosed with CLL are older than 50. The average age at
diagnosis is close to 70.
Gender. Men develop CLL more often than women.
Race/Ethnicity. B-cell CLL is more common in people of Russian and European descent,
and hardly ever develops in people from China, Japan, or Southeast Asian countries. It also
occurs commonly in black people. The reason(s) for these differences is not known.
Agent Orange. The U.S. Department of Veterans Affairs lists CLL as a disease associated
with exposure to Agent Orange, a chemical used during the Vietnam War.
Leukemia - Chronic Lymphocytic - CLL - Symptoms and Signs
Swelling of lymph nodes or glands in the neck, under the arms, or in the groin. This is a
common symptom that people with CLL usually notice first.
Discomfort or fullness in the upper left part of the abdomen, caused when the spleen
increases in size
Fever and infection
Abnormal bleeding
Shortness of breath
Weight loss
Fatigue
Chills
Night sweats
Feeling full despite not eating much
Rash
Malaise, or generally not feeling well

The following tests may be used to diagnose CLL:


Blood tests. A routine blood test called a complete blood count (CBC) is the first
test used to begin the process of diagnosing CLL. It is used to measure the
number of different types of cells in a sample of a persons blood. A person may
have CLL if the blood contains too many white blood cells, called a high white
blood cell count. The doctor will also use the blood test to find out which types of
white blood cells are increased. The CBC can also measure if a patient has a low
red blood cell count, known as anemia, and/or a low platelet count, known as
thrombocytopenia.
Bone marrow aspiration and biopsy. CLL can usually be diagnosed with blood tests
because the cancerous cells are easily found in the blood; therefore, a bone
marrow aspiration and biopsy is not needed for most patients. These two
procedures are similar and often done at the same time to examine the bone
marrow before starting treatment. Bone marrow has both a solid and a liquid part.
A bone marrow aspiration removes a sample of fluid with a needle. A bone marrow
biopsy is the removal of a small amount of solid tissue using a needle. The
sample(s) are then analyzed by a pathologist. A pathologist is a doctor who
specializes in interpreting laboratory tests and evaluating cells, tissues, and organs
to diagnose disease. A common site for a bone marrow aspiration and biopsy is
the pelvic bone, which is located in the lower back by the hip. The skin in that area
is usually numbed with medication beforehand, and other types of anesthesia
(medication to block the awareness of pain) may be used.
For some patients, a bone marrow aspiration and biopsy may be used to help
determine prognosis, which is the chance of recovery, or provide more information
about the reasons that other blood counts may be abnormal. Although a bone
marrow biopsy is usually not needed to diagnose CLL, it is often done before
beginning treatment.

Imaging tests. CLL is generally found in many parts of the body, even if
the disease has been diagnosed early. Imaging tests are rarely needed to
diagnose CLL. They are sometimes used before treatment to find all parts
of the body that are affected by CLL or to find out whether particular
symptoms may be related to CLL. Imaging tests may also be used to see
how well treatment is working.
An x-ray is a way to create a picture of the structures inside of the body,
using a small amount of radiation. It may show if cancer is growing in
lymph nodes in the chest.
A computed tomography (CT or CAT) scan creates a three-dimensional
picture of the inside of the body with an x-ray machine. A computer then
combines these images into a detailed, cross-sectional view that shows
any abnormalities. It can detect lymph nodes with CLL around the heart,
windpipe, lungs, abdomen, and pelvis. A CT scan can also be used to
measure the size of the lymph nodes. Sometimes, a special dye called a
contrast medium is given before the scan to provide better detail on the
image. This dye can be injected into a patients vein or given as a liquid to
swallow. CT scans can also help find out if CLL is in other organs, such
as the spleen.
Positron emission tomography (PET) scans have not been proven to be
helpful in diagnosing or staging CLL.

Leukemia - Chronic Lymphocytic - CLL - Stages


There is a relationship between the stage of the CLL and the prognosis. In
general, patients diagnosed at an earlier stage have better long-term survival.
Importantly, however, there is a wide range of outcomes even for patients who
have the same stage, and the stage alone cannot predict the prognosis with
certainty for each person.
Lymphocytosis, which means there are high levels of lymphocytes
Lymphadenopathy, meaning a patient has enlarged lymph nodes
Splenomegaly, which is an enlarged spleen
Anemia, meaning low levels of red blood cells
Thrombocytopenia, meaning low levels of platelets
Hepatomegaly, which is an enlarged liver
Stage 0: The patient has lymphocytosis with more than 5000 lymphocytes per
microliter of blood, but no other physical signs.
Stage I: The patient has lymphocytosis and enlarged lymph nodes. The patient
does not have an enlarged liver or spleen, anemia, or low levels of platelets.
Stage II: The patient has lymphocytosis and an enlarged spleen and/or liver and
may or may not have swollen lymph nodes.
Stage III: The patient has lymphocytosis and anemia. The patient may or may not
have swollen lymph nodes and an enlarged liver or spleen.
Stage IV: The patient has lymphocytosis and low levels of platelets. The patient
may or may not have swollen lymph nodes, an enlarged liver or spleen, or anemia.

Leukemia - Chronic Lymphocytic - CLL - Treatment Options


Chemotherapy
Chemotherapy is the use of drugs to destroy cancer cells, usually by
stopping the cancer cells ability to grow and divide. Chemotherapy is
given by a medical oncologist, a doctor who specializes in treating cancer
with medication, or a hematologist, a doctor who specializes in treating
blood disorders.
Systemic chemotherapy is delivered by mouth or through the bloodstream
to reach cancer cells throughout the body.
A standard drug that people with CLL may receive is called fludarabine
(Fludara). Similar drugs called pentostatin (Nipent) and cladribine
(Leustatin) are also sometimes used to treat CLL, although fludarabine is
used most commonly.
Chlorambucil (Leukeran) and cyclophosphamide (Neosar) can be given
orally, while cyclophosphamide can also be given intravenously.
Cyclophosphamide may be given alone or with fludarabine or with
prednisone (multiple brand names), a type of oral corticosteroid.
Today, the following drugs are often given together in combinations:
Rituximab (Rituxan) (see monoclonal antibodies below) and fludarabine
(sometimes abbreviated as FR)
Cyclophosphamide and fludarabine (called FC)
Cyclophosphamide, fludarabine and rituximab (called FCR)
Pentostatin, cyclophosphamide, and rituximab (called PCR)

Targeted therapy
Targeted therapy is a treatment that targets the leukemias specific genes,
proteins, or the tissue environment that contributes to its growth and survival. This
type of treatment blocks the growth and spread of leukemia cells while limiting
damage to healthy cells.
Monoclonal antibodies. A monoclonal antibody is a type of targeted therapy. It is
directed against a specific protein in the surface of leukemia cells, and it does not
affect cells that do not have that protein.
Rituximab is a monoclonal antibody given intravenously, that binds to a protein on
the surface of B cells, destroying some of the CLL cells and also making
chemotherapy more effective. As mentioned above, rituximab is currently being
used in combination with chemotherapy.
Alemtuzumab (Campath) is another monoclonal antibody that has been approved
by the U.S. Food and Drug Administration (FDA) as a treatment for advanced CLL
when other treatments no longer work. It can be used for both T-cell and B-cell
CLL. This antibody can be given either intravenously or as an injection under the
skin. Similarly, two new antibodies called ofatumumab (Arzerra) and obinituzumab
(Gazyva) have recently been approved for the treatment of CLL.
Kinase inhibitors. Ibrutinib (Imbruvica) is a drug called a kinase inhibitor that is
given orally which targets Brutons tyrosine kinase, an important factor influencing
the growth of B cells. Kinases are enzymes found in both normal cells and cancer
cells. Some cancer cells can be destroyed by drugs that block this particular
kinase enzyme. Ibrutinib is approved by the FDA for patients with CLL who have
already received at least one other treatment.
Idelalisib (Zydelig) is another type of kinase inhibitor. It is approved by the FDA in
combination with rituximab for patients with CLL that comes back after treatment
when rituximab alone would be considered appropriate therapy; see more below.

Side effects from chemotherapy and targeted therapy


Chemotherapy for CLL may cause hair loss and nausea and vomiting, although
nausea and vomiting can often be prevented with drugs. Doctors will also closely
watch for decreases in normal blood counts, which can increase a persons risk of
infection, bleeding, and fatigue. To manage these side effects, some patients need
transfusions of red blood cells and platelets or antibiotics to treat infections.
Sometimes, subcutaneous injections of white blood cell growth factors such as
filgrastim (Neupogen), sargramostim (Leukine), or pegfilgrastim (Neulasta) are used
to help the bone marrow make normal white blood cells. Injections of epoetin
(Epogen, Eprex, Procrit) or darbepoetin (Aranesp) may be given to treat anemia
caused by chemotherapy. However, these drugs also have risks, and it is important
for you and your doctor to carefully consider the risks and the benefits. Read more
about ASCOs recommendations for when white blood cell growth factors and epoetin
and darbepoetin treatment should be used.
Radiationtherapy

Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer
cells. A doctor who specializes in giving radiation therapy to treat cancer is called a
radiation oncologist. However, radiation therapy can be very helpful to shrink an
enlarged spleen or swollen lymph nodes and relieve symptoms.
Side effects from radiation therapy may include fatigue, mild skin reactions, upset
stomach, and loose bowel movements. Most side effects go away soon after
treatment is finished.
Surgery
Occasionally, surgery to remove the spleen, called a splenectomy may be
recommended because the spleen can become very enlarged in CLL.

Stem cell transplantation/bone marrow transplantation. A stem cell transplant is a medical


procedure in which bone marrow that contains leukemia is replaced by highly specialized
cells, called hematopoietic stem cells, that develop into healthy bone marrow. Hematopoietic
stem cells are blood-forming cells found both in the bloodstream and in the bone marrow.
Today, this procedure is more commonly called a stem cell transplant, rather than bone
marrow transplant, because it is the stem cells in the blood that are typically being
transplanted, not the actual bone marrow tissue.
There are two types of stem cell transplantation depending on the source of the replacement
blood stem cells: allogeneic (ALLO) and autologous (AUTO). ALLO uses donated stem cells,
while AUTO used the patients own stem cells. ALLO is the type of transplant used for treating
CLL and is typically considered for younger patients either when the standard treatments
have not worked well or the patient has a high risk of the CLL returning more quickly. The
goal is to destroy all of the cancer cells in the marrow, blood, and other parts of the body
using high doses of chemotherapy and/or radiation therapy and then allow replacement blood
stem cells to create healthy bone marrow.
Leukemia - Chronic Lymphocytic - CLL - Latest Research
New drugs and drug combinations. Researchers are working to find new drugs for CLL.
Different combinations of chemotherapy and targeted therapy are also being studied as a
way to increase the likelihood that a patient will have a complete remission and live longer.
There are many new drugs for CLL being evaluated in clinical trials for patients with recurrent
CLL with the hope of testing some of these drugs as initial therapy in the near future.
Researchers are also looking at combining ibrutinib with bendamustine and ofatumumab.
Idelalisib is being studied in combination with bendamustine, rituximab, and ofatumumab.
Flavopiridol is a drug given intravenously that is being studied as a treatment for CLL when
few standard treatments have helped control the disease.
Xm5574 is a monoclonal antibody also being researched for treatment of CLL.