Hodgkin Lymphoma Cells

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.

Weakened immune system: The risk of developing Hodgkin lymphoma may be increased by having a weakened immune system (such as from an inherited condition or certain drugs used after an organ transplant).

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

Weight loss  for no known reason

Fever  that does not go away

Soaking night sweats

Itchy  skin

Coughing , trouble breathing, or chest pain

Weakness  and tiredness that don't go away

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 Reed-Sternberg cell.

Types of Hodgkin Lymphoma

When Hodgkin lymphoma is found, the pathologist reports the type. There are two major types of Hodgkin lymphoma:

Classical Hodgkin lymphoma: Most people with Hodgkin lymphoma have the classical type. The Reed-Sternberg cell looks like the photo.

Nodular lymphocyte-predominant Hodgkin lymphoma: This is a rare type of Hodgkin lymphoma. The abnormal cell is called a popcorn cell. It may be treated differently from the classical type.

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:

CT scan : An x-ray machine linked to a computer takes a series of detailed pictures of your chest, abdomen, and pelvis. You may receive an injection of contrast material. Also, you may be asked to drink another type of contrast material. The contrast material makes it easier for the doctor to see swollen lymph nodes and other abnormal areas on the x-ray.

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:

The number of lymph nodes that have Hodgkin lymphoma cells

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.

The stages of Hodgkin lymphoma are as follows:

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.

Recurrent: The disease returns after treatment.

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.

B: You have 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)

Its stage (where the lymphoma is found)

Whether you have a tumor that is more than 4 inches (10 centimeters) wide

Your age

Whether you've had weight loss, drenching night sweats, or fevers.

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

Non-Hodgkin's lymphoma facts

NHL is a cancer that originates in the lymphatic system.

About 66,000 patients are diagnosed yearly, and approximately 18,000 patients die of NHL yearly in the U.S.

There are several subtypes of NHL, each requiring different treatments.

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.

What is non-Hodgkin's lymphoma?

Non-Hodgkin's lymphoma is a type of cancer that originates in the lymphatic system. It is estimated to be the sixth most common cancer in the United States. The lymphatic system is part of the body's immune system and helps fight infections and other diseases. In addition, the lymphatic system filters out bacteria, viruses, and other unwanted substances.

What causes non-Hodgkin's lymphoma?

We don't know what causes non-Hodgkin's lymphoma (NHL). NHL occurs when your body produces too many abnormal lymphocytes. In the normal life cycle of lymphocytes (a type of white blood cell), old lymphocytes die and your body creates new ones to replenish the supply. In NHL, lymphocytes grow indefinitely, so the number of circulating lymphocytes increases, filling up the lymph nodes and causing them to swell.

In NHL, either B cells or T cells are involved in this process. These are the two subtypes of lymphocytes.

B cells produce antibodies that fight infections. This is the most common type of cell involved in NHL.

T cells kill the foreign substances directly. NHL less frequently originates from T cells.

The following are some of the common subtypes of NHL:

Burkitt's lymphoma: This lymphoma has two major subtypes, an African type closely associated with an infection with the Epstein-Barr virus and the non-African, or sporadic, form that is not linked to the virus.

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.

What are risk factors for non-Hodgkin's lymphoma?

In many cases, people who develop NHL have no risk factors, and doctors seldom know why one person develops non-Hodgkin's lymphoma and another does not.

Certain risk factors increase the chance that a person will develop this disease although most people who have these risk factors will never develop the disease.

Risk factors

Medications that suppress your immune system: Using immunosuppressive agents (such as after an organ transplant) is a risk factor as it reduces your bodies ability to fight infection.

Weakened immune system: The risk of developing lymphoma may be increased by having a weakened immune system.

Certain infections: Certain viral and bacterial infections increase the risk of NHL. Examples are HIV, hepatitis C virus, and Epstein-Barr virus. A type of bacteria sometimes linked to NHL is the ulcer-causing H. pylori.

Note: Lymphoma is not contagious. You cannot catch lymphoma from another person.

Age: Although non-Hodgkin's lymphoma can occur in young people, the chance of developing this disease increases with age. Most people with non-Hodgkin's lymphoma are older than 60 years of age.

Other possible links: People who work with herbicides or certain other chemicals may be at increased risk of this disease. Researchers are also looking at a possible link between using hair dyes before 1980 and non-Hodgkin's lymphoma. None of these possible links have definitely been proven.

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.

What are symptoms and signs of non-Hodgkin's lymphoma?

Signs and symptoms of NHL include the following:

Swollen, painless lymph nodes  in the neck, armpits, or groin

Unexplained weight loss

Fever

Night sweats

Coughing , trouble breathing, or chest pain

Weakness  and tiredness that don't go away (fatigue)

Abdominal pain  or swelling, or a feeling of fullness in the abdomen

Itching  of the skin

How is non-Hodgkin's lymphoma diagnosed?

Physical exam: Your doctor will complete a physical examination with a special emphasis on palpating your lymph nodes in your neck, underarms, and groin and establishing if they are swollen. He or she will also try to find out if your spleen or liver are swollen. In most cases, swollen lymph nodes are signs of infection (rather then lymphoma), and your doctor will try to establish if you have any other signs of infection and what the source of the infection could be.

Medical history: You will be asked questions in regards to your past medical history and about risk factors for NHL.

Blood tests: A complete blood count (CBC) will usually be performed to check the number of white blood cells. Additional tests might include a lactate dehydrogenase level (can be elevated in lymphoma). Additional tests might be performed to rule out an infection causing the swollen lymph nodes.

Imaging procedures: A chest X-ray or CT scan of the chest or neck might help detect the presence of tumors or more enlarged lymph nodes. Positron emission tomography (PET) scanning is a newer modality to help detect NHL.

Biopsy: Your doctor might recommend a biopsy of lymph nodes to diagnose the cause of the swelling. The samples will then be given to a pathologist who will review the sample under the microscope and establish a diagnosis.

There are three ways to diagnose a lymph node: removal of the entire lymph node (excisional biopsy); partial removal of a lymph node (incisional biopsy);fine-needle aspiration (using a thin needle to remove some lymph node tissue) is often not diagnostic as not enough tissue is removed for the pathologist to make a diagnosis.

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 non-Hodgkin'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:

Bone marrow biopsy (see above)

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.

What is the treatment for non-Hodgkin's lymphoma?

Your doctor will usually refer you to an oncologist for evaluation and treatment. Some large academic medical centers have oncologists who specialize in lymphomas.

The treatment plan depends mainly on the following:

The type of non-Hodgkin's lymphoma

Its stage (where the lymphoma is found)

How quickly the cancer is growing

The patient's age

Whether the patient has other health problems

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.

What is the prognosis and survival rate for non-Hodgkin's lymphoma?

The prognosis of NHL can be good but is linked to the type of lymphoma, the extent of spread (staging), and response to therapy. Prognosis should be discussed with the patient's health-care provider.

Approximately 66,000 patients were diagnosed with non-Hodgkin's lymphoma in 2011, and about 18,000 patients died in 2011.

Five-year survival is a measure used to predict and gauge the severity of the cancer. Please discuss your own risk factors, staging, and classifications with your own health-care team as none of these numbers should be applied to an individual patient without considering all the circumstances of the patient's illness.

The National Cancer Institute reports the following average five-year survival:

Stage at diagnosisStage distribution (%)

5-year relative survival (%)

Localized (confined to primary site)

29 81.1

Regional (spread to regional lymph nodes)

15 70.5

Distant (cancer has metastasized)

48 58.5

Unknown (unstaged) 8 64.1

Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many immature lymphocytes (a type of white blood cell).

Childhood acute lymphoblastic leukemia (also called acute lymphocyticleukemia or ALL) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated. It is the most common type of cancer in children.

Normally, the bone marrow makes blood stem cells (immature cells) that develop into mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.

The myeloid stem cell develops into one of three types of mature blood cells:

Red blood cells that carry oxygen and other materials to all tissues of the body.

Platelets that help prevent bleeding by causing blood clots to form.

Granulocytes (white blood cells) that fight infection and disease.

The lymphoid stem cell develops into a lymphoblast cell and then into one of three types of lymphocytes (white blood cells):

B lymphocytes that make antibodies to help fight infection.

T lymphocytes that help B lymphocytes make the antibodies that help fight infection.

Natural killer cells that attack cancer cells and viruses.

Blood cell development. A blood stem cell goes through several steps to become a red blood cell,

platelet, or white blood cell.

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.

There are subgroups of childhood ALL.

There are different subgroups of ALL based on the following:

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).

Whether there are certain changes in the chromosomes. Philadelphia chromosome -positive ALL is one type of chromosome change that may occur.

Family history and exposure to radiation may affect the risk of developing childhood ALL.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Possible risk factors for ALL include the following:

Having a brother or sister with leukemia.

Being white or Hispanic.

Living in the United States.

Being exposed to x-rays before birth.

Being exposed to radiation.

Past treatment with chemotherapy or other drugs that weaken the immune system.

Having certain changes in genes or genetic disorders, such as Down syndrome.

Possible signs of childhood ALL include fever and bruising.

These and other symptoms may be caused by childhood ALL. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

Fever .

Easy bruising  or bleeding.

Petechiae (flat, pinpoint, dark-red spots under the skin caused by bleeding).

Bone or joint pain.

Painless lumps in the neck, underarm, stomach, or groin.

Pain or feeling of fullness below the ribs.

Weakness , feeling tired, or looking pale.

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 number of red blood cells and platelets.

o The number and type of white blood cells.

o The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.

o The portion of the sample made up of red blood cells.

Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells,

and platelets are counted. The CBC is used to test for, diagnose, and monitor

many different conditions.

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.

Bone marrow aspiration and biopsy. After a

small area of skin is numbed, a Jamshidi needle (a long, hollow needle) is inserted into

the patient's hip bone. Samples of blood, bone, and bone marrow are removed for

examination under a microscope.

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.

Philadelphia chromosome. A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The bcr-abl gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called the Philadelphia

chromosome.

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.

Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.

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.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options may depend on:

Age at diagnosis and race.

How quickly and how low the leukemia cell count drops after initial treatment.

Whether the leukemia cells began from B lymphocytes or T lymphocytes.

Whether there are certain changes in the chromosomes of lymphocytes.

Whether the leukemia has spread to the brain and spinal cord.

Whether the child has Down syndrome.

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.

In childhood ALL, risk groups are used instead of stages.

Because ALL is a disease of the blood cells, it has already spread throughout the body at diagnosis. There is no staging system for ALL. Risk groups are used to plan treatment.

Risk groups are described as:

Standard (low) risk: Includes children aged 1 to 9 years who have a white blood cell count of less than 50,000/µL 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/µL or more at diagnosis.

Other factors that affect the risk group include the following:

Whether the leukemia cells formed from B lymphocytes or T lymphocytes.

Whether there are certain changes in the chromosomes of the lymphocytes.

How quickly the leukemia responds to initial therapy.

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.

Recurrent Childhood Acute Lymphoblastic Leukemia

Recurrent childhood ALL is cancer that has recurred (come back) after it has been treated. The leukemia may come back in the blood and bone marrow, brain, testicles, spinal cord, or in other parts of the body.

There are different types of treatment for childhood acute lymphoblastic leukemia (ALL).

Different types of treatment are available for children with acute lymphoblastic leukemia (ALL). Some treatments are standard (the currently used treatment), and some are being tested

in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Children with ALL should have their treatment planned by a team of doctors with expertise in treating childhood leukemia.

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.

Pediatric nurse specialist.

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).

Stem cell transplant (Step 1). Blood is taken from a vein in the arm of the donor. The

patient or another person may be the donor. The blood flows through a machine that

removes the stem cells. Then the blood is returned to the donor through a vein in the

other arm.

Stem cell transplant (Step 2). The patient receives

chemotherapy to kill blood-forming cells. The patient may receive radiation therapy (not

shown).

Stem cell transplant (Step 3). The patient receives stem cells through a catheter

placed into a blood vessel in the chest.

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.