Hodgkin lymphoma begins when a lymphocyte (usually a B cell) becomes abnormal. The
abnormal cell is called a Reed-Sternberg cell. (See photo below.)
The Reed-Sternberg cell divides to make copies of itself. The new cells divide again and again,
making more and more abnormal cells. The abnormal cells don't die when they should. They
don't protect the body from infections or other diseases. The buildup of extra cells often forms a
mass of tissue called a growth or tumor.
See the Staging section for information about Hodgkin lymphoma that has spread
Risk factors
Doctors seldom know why one person develops Hodgkin lymphoma and another does not. But
research shows that certain risk factors increase the chance that a person will develop this
disease.
The risk factors for Hodgkin lymphoma include the following:
Certain viruses: Having an infection with the Epstein-Barr virus (EBV) or thehuman
immunodeficiency virus (HIV) may increase the risk of developing Hodgkin lymphoma.
However, lymphoma is not contagious. You can't catch lymphoma from another person.
Age: Hodgkin lymphoma is most common among teens and adults aged 15 to 35 years
and adults aged 55 years and older.
Family history: Family members, especially brothers and sisters, of a person with
Hodgkin lymphoma or other lymphomas may have an increased chance of developing this
disease.
Having one or more risk factors does not mean that a person will develop Hodgkin lymphoma.
Most people who have risk factors never develop cancer.
Symptoms
Hodgkin lymphoma can cause many symptoms:
Swollen lymph nodes (that do not hurt) in the neck, underarms, or groin
Becoming more sensitive to the effects of alcohol or having painful lymph nodes after
drinking alcohol
Itchy skin
Most often, these symptoms are not due to cancer. Infections or other health problems may also
cause these symptoms. Anyone with symptoms that last more than 2 weeks should see a doctor
so that problems can be diagnosed and treated.
Diagnosis
If you have swollen lymph nodes or another symptom that suggests Hodgkin lymphoma, your
doctor will try to find out what's causing the problem. Your doctor may ask about your personal
and family medical history.
You may have some of the following exams and tests:
Physical exam: Your doctor checks for swollen lymph nodes in your neck, underarms,
and groin. Your doctor also checks for a swollen spleen or liver.
Blood tests: The lab does a complete blood count to check the number of white blood
cells and other cells and substances.
Chest x-rays: X-ray pictures may show swollen lymph nodes or other signs of disease in
your chest.
Biopsy: A biopsy is the only sure way to diagnose Hodgkin lymphoma. Your doctor may
remove an entire lymph node (excisional biopsy) or only part of a lymph node (incisional
biopsy). A thin needle (fine needle aspiration) usually cannot remove a large enough sample
for the pathologist to diagnose Hodgkin lymphoma. Removing an entire lymph node is best.
The pathologist uses a microscope to check the tissue for Hodgkin lymphoma cells. A person
with Hodgkin lymphoma usually has large, abnormal cells known as Reed-Sternberg cells.
They are not found in people with non-Hodgkin lymphoma. See the photo of a ReedSternberg cell.
Classical Hodgkin lymphoma: Most people with Hodgkin lymphoma have the classical
type. The Reed-Sternberg cell looks like the photo.
Staging
Your doctor needs to know the extent (stage) of Hodgkin lymphoma to plan the best treatment.
Staging is a careful attempt to find out what parts of the body are affected by the disease.
Hodgkin lymphoma tends to spread from one group of lymph nodes to the next group. For
example, Hodgkin lymphoma that starts in the lymph nodes in the neck may spread first to the
lymph nodes above the collarbones, and then to the lymph nodes under the arms and within the
chest.
In time, the Hodgkin lymphoma cells can invade blood vessels and spread to almost any other
part of the body. For example, it can spread to the liver, lungs, bone, and bone marrow.
Staging may involve one or more of the following tests:
MRI: A powerful magnet linked to a computer is used to make detailed pictures of your
bones, brain, or other tissues. Your doctor can view these pictures on a monitor and can print
them on film.
PET scan: You receive an injection of a small amount of radioactive sugar. A machine
makes computerized pictures of the sugar being used by cells in your body. Lymphoma cells
use sugar faster than normal cells, and areas with lymphoma look brighter on the pictures.
Bone marrow biopsy: The doctor uses a thick needle to remove a small sample of bone
and bone marrow from your hipbone or another large bone. Local anesthesia can help control
pain. A pathologist looks for Hodgkin lymphoma cells in the sample.
Other staging procedures may include biopsies of other lymph nodes, the liver, or other tissue.
The doctor considers the following to determine the stage of Hodgkin lymphoma:
Whether these lymph nodes are on one or both sides of the diaphragm (see picture)
Whether the disease has spread to the bone marrow, spleen, liver, or lung.
Stage I: The lymphoma cells are in one lymph node group (such as in the neck or
underarm). Or, if the lymphoma cells are not in the lymph nodes, they are in only one part of a
tissue or an organ (such as the lung).
Stage II: The lymphoma cells are in at least two lymph node groups on the same side of
(either above or below) the diaphragm. Or, the lymphoma cells are in one part of a tissue or
an organ and the lymph nodes near that organ (on the same side of the diaphragm). There
may be lymphoma cells in other lymph node groups on the same side of the diaphragm.
Stage III: The lymphoma cells are in lymph nodes above and below the diaphragm.
Lymphoma also may be found in one part of a tissue or an organ (such as the liver, lung, or
bone) near these lymph node groups. It may also be found in the spleen.
Stage IV: Lymphoma cells are found in several parts of one or more organs or tissues.
Or, the lymphoma is in an organ (such as the liver, lung, or bone) and in distant lymph nodes.
In addition to these stage numbers, your doctor may also describe the stage as A or B:
A: You have not had weight loss, drenching night sweats, or fevers.
Treatment
Your doctor can describe your treatment choices and the expected results. You and your doctor
can work together to develop a treatment plan that meets your needs.
Your doctor may refer you to a specialist, or you may ask for a referral. Specialists who treat
Hodgkin lymphoma include hematologists, medical oncologists, and radiation oncologists . Your
doctor may suggest that you choose an oncologist who specializes in the treatment of Hodgkin
lymphoma. Often, such doctors are associated with major academic centers. Your health care
team may also include an oncology nurse and a registered dietitian.
The choice of treatment depends mainly on the following:
The type of your Hodgkin lymphoma (most people have classical Hodgkin lymphoma)
Whether you have a tumor that is more than 4 inches (10 centimeters) wide
Your age
People with Hodgkin lymphoma may be treated with chemotherapy, radiation therapy, or both.
If Hodgkin lymphoma comes back after treatment, doctors call this a relapse or recurrence.
People with Hodgkin lymphoma that comes back after treatment may receive high doses of
chemotherapy, radiation therapy, or both, followed by stem cell transplantation.
You may want to know about side effects and how treatment may change your normal activities.
Because chemotherapy and radiation therapy often damage healthy cells and tissues, side
effects are common. Side effects may not be the same for each person, and they may change
from one treatment session to the next. Before treatment starts, your health care team will
explain possible side effects and suggest ways to help you manage them. The younger a person
is, the easier it may be to cope with treatment and its side effects.
At any stage of the disease, you can have supportive care. Supportive care is treatment to
prevent or fight infections, to control pain and other symptoms, to relieve the side effects of
therapy, and to help you cope with the feelings that a diagnosis of cancer can bring.
You may want to talk to your doctor about taking part in a clinical trial, a research study of new
treatment methods. See the Taking Part in Cancer Research section
About 66,000 patients are diagnosed yearly, and approximately 18,000 patients die of
NHL yearly in the U.S.
Symptoms include swollen lymph nodes, weight loss,fever, and night sweats.
NHL is staged on a 1-4 scale with A (no associated symptoms like fever, weight loss, or
night sweats) and B subtypes.
Staging the cancer is important to determine treatment and predict the outcome of
treatment.
Depending on the stage and type of NHL, treatment can include chemotherapy,biological
therapy, stem cell transplant, and/or radiation therapy.
Diffuse large cell lymphoma: This represents the most common lymphoma (approximately 30%
of NHL) and can be rapidly fatal if not treated.
Follicular lymphoma: These lymphomas exhibit a specific growth pattern when viewed under
the microscope (follicular or nodular pattern); they are usually advanced at the time of diagnosis.
MALT lymphoma: This is a B cell lymphoma that usually affects individuals in their 60s. The
most common area for this lymphoma to develop is the stomach.
Mantle cell lymphoma: One of the rarest of the NHL, mantle cell lymphoma accounts for about
6% of cases. This NHL is difficult to treat and is a subtype of B cell lymphoma.
Adult T cell lymphoma/leukemia: This is a rare but aggressive NHL of the immune system's T
cells. Human T cell leukemia/lymphotropic virus type (HTLV-1) is believed to be the cause.
Note: Having one or more risk factors does not mean that a person will develop non-Hodgkin's
lymphoma. Most people who have risk factors never develop cancer.
Fever
Night sweats
Bone marrow biopsy: A bone marrow biopsy can establish the spread of the disease. This
involves the insertion of a needle into bone to obtain bone marrow. In adults, the most common
site for this biopsy is the pelvic bone.
What are the types of non-Hodgkin's lymphoma, and how is nonHodgkin's lymphoma staging determined?
NHL is classified into many different types. Several classification systems exist for NHL, including
the Revised European American Lymphoma Classification which is the foundation for the WHO
lymphoma classification. The classifications uses cell types and defining other characteristics.
Basically there are three large groups: the B cell, T cell, and natural killer cell tumors.
Newer techniques such as immunophenotyping (a way to study the proteins on a cell and identify
the precise types of B or T cells that are involved) are used to diagnose and classify lymphomas.
This technique is especially useful in the case of B cell lymphomas.
Testing of DNA from the lymphoma is used to detect gene defects that help determine the
prognosis and response to treatment.
To plan the best treatment for NHL, your health-care provider needs to stage (know the extent of)
the disease. This is an attempt to find out what part of your body is involved.
Different tests are involved in the staging process, and they can include the following:
CT scan
MRI
Ultrasound
PET scan: Radioactive material is injected, and a CT scan is performed to determine the
metabolism of this material. Lymphoma cells show faster metabolism than normal cells, and
areas with lymphoma look brighter on the pictures.
Doctors will also stage the lymphoma based on spread of the disease and organ involvement as
well as symptoms:
Stage I: The cells are found in only one lymph node area (such as in the neck or axilla).
Or, if the abnormal cells are not in the lymph nodes, they are in only one part of a tissue or
organ (such as the lung, but not the liver or bone marrow).
Stage II: The lymphoma cells are found in at least two lymph node areas on the same
side of the body or only above or below the diaphragm. Or the cells are in one organ and the
lymph nodes affected are near that organ
Stage III: The lymphoma is in lymph nodes above and below the diaphragm. There might
be spread into an organ near this lymph node group.
Stage IV: In addition to lymph cell spread, lymphoma cells are found in several parts of
one or more organs or tissues.
A: No symptoms (You have not had weight loss, fever or night sweats)
B: Presence of any of the following symptoms: weight loss (10 % or more in the last six
months), fever (greater then 101.5 F) night sweats, or severe itching.
If there are symptoms present such as fever and night sweats (see above)
If you have a slow-growing non-Hodgkin's lymphoma without symptoms, you may not require
treatment for the cancer right away. You will be watched closely by your health-care team. These
cancers might not require treatment for years, although close follow-up is necessary. If the
indolent lymphoma produces symptoms, therapy will usually consist
of chemotherapy and biological therapy. Stage I and II often require radiation therapy.
For an aggressive type of lymphoma, a combination of chemotherapy and biological therapy is
usually indicated, and sometimes radiation therapy will be added.
If treatment is required, there are several options that are utilized alone or in combination:
Chemotherapy: This is a drug treatment either as an injection or oral form that kills cancer cells.
This treatment can involve one medication or multiple medications and be given alone or in
conjunction with other therapies. This therapy is given in cycles, alternating treatment periods
and nontreatment periods. The repetition of these cycles and the number of cycles will be
determined by your oncologist based on the staging of your cancer and the medications used.
Chemotherapy also harms normal cells that divide rapidly. This can lead to hair loss, GI
symptoms, and difficulty with your immune system.
Radiation therapy: High doses of radiation are used to kill cancer cells and shrink tumors. This
modality can be used alone or in conjunction with other therapies. Side effects usually depend on
the type and dosage of the therapy as well as the area undergoing radiation therapy. Universally,
patients tend to get tired during radiation therapy, especially toward the later stages of treatment.
Stem cell transplant: This procedure allows you to receive large doses of chemotherapy or
radiation therapy to kill the lymphoma cells that might not be killed with standard levels of
therapy. This therapy is used if your lymphoma returns after treatment. For this therapy, you need
to be admitted to the hospital. After the therapy, healthy stem cells (that were either taken from
you before the therapy or from a donor) are injected to form a new immune system.
Biological drugs: These are medications that enhance your immune system's ability to fight
cancers. In NHL, monoclonal antibodies are used for treatment. The therapy is administered via
an IV, and the monoclonal antibodies bind to the cancer cells and augment the immune system's
ability to destroy cancer cells. Rituximab (Rituxan) is such a drug used in the treatment of B cell
lymphoma. Side effects for this treatment are usually flu-like symptoms. Rarely, a person can
have a severe reaction, including a drop in blood pressure or difficulty breathing.
Radio immunotherapy medications: These are made of monoclonal antibodies that transport
radioactive materials directly to cancer cells. Because the radioactive material is traveling and
binding directly to the cancer cell, more radiation is delivered to the cancer cell and less to the
normal tissue. Ibritumomab (Zevalin) and tositumomab (Bexxar) are two drugs approved for this
use in lymphomas. Side effects usually include getting very tired or experiencing flu-like
symptoms.
Additional aspects of cancer treatments
In addition to medical therapies, patients will also require supportive care. You should have the
opportunity to learn about your disease and the treatment options and discuss this with your care
team. Most cancer centers will have support groups where you can share your concerns with
other patients and learn from their experiences.
Some patients find moderate physical activity helpful. You should discuss with your doctor what
kind of activities are appropriate.
Eating the appropriate amounts of foods, as well as the right foods, is an important part of your
treatment. Speaking with a nutritionist can be very helpful.
In addition, vitamin deficiencies (especially vitamin D) have recently been linked to worse survival
in some subgroups of cancer patients. Patients should discuss their nutritional requirements with
their health-care team.
Appropriate caloric intake is important especially if nausea is present as a result of your
treatments. Some people find that exercise can help their nausea during
therapy. Acupuncture has also shown to decrease the side effects of cancer treatments.
Stage at diagnosis
Stage
distribution
(%)
Localized (confined to 29
5-year relative
survival (%)
81.1
primary site)
Regional (spread to
15
regional lymph nodes)
70.5
48
58.5
Unknown (unstaged)
64.1
Red blood cells that carry oxygen and other materials to all tissues of the body.
The lymphoid stem cell develops into a lymphoblast cell and then into one of three types of
lymphocytes (white blood cells):
T lymphocytes that help B lymphocytes make the antibodies that help fight infection.
In ALL, too many stem cells develop into lymphoblasts and do not mature to become
lymphocytes. These lymphoblasts are called leukemia cells. The leukemia cells do not work like
normal lymphocytes and are not able to fight infection very well. Also, as the number of leukemia
cells increases in the blood and bone marrow, there is less room for healthy white blood cells,
red blood cells, and platelets. This may lead to infection, anemia, and easy bleeding.
Whether the type of blood cell that is affected looks more like a B lymphocyte or a T
lymphocyte.
The age of the child at diagnosis. For example, whether the child is younger than one
year, one year to 10 years old, or older than 10 years (teenager).
Past treatment with chemotherapy or other drugs that weaken the immune system.
Fever.
Petechiae (flat, pinpoint, dark-red spots under the skin caused by bleeding).
Loss of appetite.
Tests that examine the blood and bone marrow are used to detect (find)
and diagnose childhood ALL.
The following tests and procedures may be used:
Physical exam and history: An exam of the body to check general signs of health,
including checking for signs of disease, such as lumps or anything else that seems unusual. A
history of the patient's health habits and past illnesses and treatments will also be taken.
Complete blood count (CBC) with differential: A procedure in which a sample of blood is
drawn and checked for the following:
o
The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small
piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views
the bone marrow, blood, and bone under a microscope to look for signs of cancer.
Cytogenetic analysis: A laboratory test in which the cells in a sample of blood or bone
marrow are viewed under a microscope to look for certain changes in the chromosomes in the
lymphocytes. For example, in Philadelphia chromosome-positive ALL, part of one
chromosome is moved to another chromosome. This is called the Philadelphia
chromosome. Other tests, such as fluorescence in situ hybridization (FISH), may also be
done to look for certain changes in the chromosomes.
Immunophenotyping: A test in which the cells in a sample of blood or bone marrow are
looked at under a microscope to find out if malignant lymphocytes (cancer) began from the B
lymphocytes or the T lymphocytes.
Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of
energy beam that can go through the body and onto film, making a picture of areas inside the
body.
How quickly and how low the leukemia cell count drops after initial treatment.
Whether the leukemia has spread to the brain and spinal cord.
If leukemia recurs (comes back) after initial treatment, the prognosis and treatment options may
depend on:
How long it is between the end of initial treatment and when the leukemia recurs.
Whether the leukemia recurs in the bone marrow or outside the bone marrow.
Standard (low) risk: Includes children aged 1 to 9 years who have a white blood cell
count of less than 50,000/L at diagnosis.
High risk: Includes children younger than 1 year or older than 9 years and children who
have a white blood cell count of 50,000/L or more at diagnosis.
Other factors that affect the risk group include the following:
It is important to know the risk group in order to plan treatment. Children with high risk ALL
usually receive more aggressive treatment than children with standard risk ALL.
Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children
with cancer. The pediatric oncologist works with other pediatric health professionals who are
experts in treating children with leukemia and who specialize in certain areas of medicine. These
may include the following specialists:
Hematologist.
Medical oncologist.
Pediatric surgeon.
Radiation oncologist.
Endocrinologist.
Neurologist.
Pathologist.
Radiologist.
Social worker.
Rehabilitation specialist.
Psychologist.
Regular follow-up exams are very important. Side effects can result from treatment long after it
ends. These are called late effects. Radiation therapyto the head may affect the child's
developing brain and cause changes in mood, feelings, thinking, learning, or memory. Late
effects of treatment for ALL also include the risk of second cancers (new types of cancer),
especially brain tumors. Early diagnosis and treatment of these secondary brain tumors may help
lower the risk from these brain tumors. Children younger than 4 years have a higher risk of side
effects from radiation therapy to the brain. It is important to talk with your child's doctors about
the possible late effects caused by some treatments.
The treatment of childhood ALL usually has 3 phases.
The treatment of childhood ALL is done in phases:
Induction therapy: This is the first phase of treatment. Its purpose is to kill the leukemia
cells in the blood and bone marrow. This puts the leukemia into remission. This is also called
the remission induction phase.kortikosteroid -> mengurangi sel2 blastoidnya,
Consolidation /intensification therapy: This is the second phase of therapy. It begins once
the leukemia is in remission. The purpose of consolidation/intensification therapy is to kill any
remaining leukemia cells that may not be active but could begin to regrow and cause a
relapse.
Maintenance therapy: This is the third phase of treatment. Its purpose is to kill any
remaining leukemia cells that may regrow and cause a relapse. Often the cancer treatments
are given in lower doses than those used for induction and consolidation/intensification
therapy. This is also called the continuation therapy phase.
Bone marrow biopsy and aspirates are done throughout all phases to see how well the leukemia
is responding to treatment.
Treatment called central nervous system (CNS) sanctuary therapy is usually given during
induction therapy and consolidation/intensification therapy and is often given during maintenance
therapy. Because most anticancer drugs given by mouth or injected into a vein to kill leukemia
cells may not reach leukemia cells in the CNS (brain and spinal cord), the leukemia cells are able
to find sanctuary (hide) in the CNS. Certain anticancer drugs, intrathecal chemotherapy, and
radiation therapy to the brain are able to reach leukemia cells in the CNS and are given to kill the
leukemia cells and prevent the cancer from recurring (coming back). CNS sanctuary therapy is
also called CNS prophylaxis because it is given to stop leukemia cells from growing in the CNS.
Four types of standard treatment are used:
Chemotherapy
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by
killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or
injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells
throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the
cerebrospinal fluid (intrathecal), an organ, or a body cavity such as the abdomen, the drugs
mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is
treatment using more than one anticancer drug. The way the chemotherapy is given depends on
the type of the cancer being treated.
Intrathecal chemotherapy or high doses of chemotherapy injected into a vein may be used to
treat childhood ALL that has spread, or may spread, to the brain and spinal cord. When used to
prevent cancer from spreading to the brain and spinal cord, it is called central nervous system
(CNS) sanctuary therapy or CNS prophylaxis. CNS sanctuary therapy is given in addition to
chemotherapy by mouth or vein that is intended to kill leukemia cells in the rest of the body. All
children with ALL receive CNS sanctuary therapy as part of their treatment.
Radiation therapy
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation
to kill cancer cells or keep them from growing. There are two types of radiation therapy. External
radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal
radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that
are placed directly into or near the cancer. External radiation therapy may be used to treat
childhood ALL that has spread, or may spread, to the brain and spinal cord. When used this way,
it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis.
Because radiation therapy to the brain can affect growth and brain development in young
children, many children with ALL are treated without radiation therapy. Radiation therapy to the
brain and spinal cord is sometimes used as CNS sanctuary therapy to treat children and
teenagers in the high risk group. Clinical trials are studying new ways of using radiation therapy
that may have fewer side effects, including giving lower doses of radiation.
Chemotherapy with stem cell transplant
Stem cell transplant is a method of giving very high doses of chemotherapy and sometimes
radiation therapy, and then replacing the blood-forming cells destroyed by the cancer treatment.
Stem cells (immature blood cells) are removed from the blood or bone marrow of a donor. After
the patient receives very high doses of chemotherapy and sometimes radiation therapy, the
donor's stem cells are given back to the patient through an infusion. These reinfused stem cells
grow into (and restore) the patient's blood cells. A stem cell transplant may use stem cells from a
donor who is or is not related to the patient.
Stem cell transplant is rarely used as initial treatment for children and teenagers with ALL. It is
used more often as part of treatment for ALL that relapses (comes back after treatment).
Targeted therapy
Targeted therapy is a treatment that uses drugs or other substances to identify and attack
specific cancer cells without harming normal cells.
Tyrosine kinase inhibitors (TKIs) are targeted therapy drugs that block the enzyme, tyrosine
kinase, which causes stem cells to develop into more white blood cells (granulocytes or blasts)
than the body needs. For example, imatinib mesylate (Gleevec) is a TKI used in the treatment of
children with Philadelphia chromosome -positive ALL.