About Burkitt’s Lymphoma

BASICS:

Lymphoma and Leukemia are very similar. They both attack the immune system. The primary difference is just how they process through the body.

Lymphomas fall into two categories, Hodgkin's, and the more serious Non-Hodgkin's --- Burkitt's Lymphoma falls under the umbrella of Non-Hodgkin's Lymphomas that is sometimes called a B-cell lymphoma, or small non-cleaved cell lymphoma.

There are two general types of Burkitt's Lymphoma: Endemic and Sporadic.
Endemic (characteristic of a specific place) affects primarily children of African decent - it is the most common childhood cancer in Africa.
The much less common version, Sporadic (occurring in scattered instances) is the type here in the United States, and is what Johanna battled.
It is a very rare and extremely aggressive killer-cancer in the lymphatic system (part of the immune system, it functions to fight disease and infections).

In the United States, there are only about 300 (that’s right, only about 300) cases of Burkitt's Lymphoma reported each year.
It usually attacks children ages 4-20; most commonly boys – it rarely attacks girls.
In most cases the children are healthy and active with no prior symptoms or existing conditions.
Researchers have been unable to find any true connection to genetics, lifestyle, viruses, etc.
It is the fastest growing cancer known, capable of doubling in size every 14 hours; the number of new cases of this tumor is rising in most countries.
It is commonly misdiagnosed for several months, usually as a stomach flu, irritable bowel syndrome, colitis, or Crohn’s Disease.

The Sporadic Form of Burkitt’s Lymphoma
In the Sporadic form of Burkitt's Lymphoma, patients are likely to have an abdominal swelling, often in the area of the ileocecal valve (the valve between the lower portion of the small intestine and the beginning of the large intestine). About 90% of American children with Burkitt's Lymphoma have abdominal tumors. Others may develop tumors in the testes, ovaries, skin, nasal sinuses, or lymph nodes. In adults, Burkitt's Lmphoma frequently produces a bulky abdomen and may involve the liver, spleen, and bone marrow.

Demographics
In the United States, Burkitt's Lymphoma is more common in male than in female children. The non-Hodgkin's lymphomas as a group account for about 7% of cancers in persons under 20 years of age. Between 40% and 50% of these cases is Burkitt's Lymphoma; only about 300 cases each year are reported.
In adults, Burkitt's lymphoma is again more common in males than in females. It is 1,000 times more common in persons with AIDS than in the general population. Currently, about 2% of AIDS patients develop Burkitt's lymphoma. The majority of these patients have stage IV disease by the time the tumor is diagnosed.

Causes – Oncogenes:
Burkitt's Lymphoma affects a part of the immune system known as the lymphatic or lymphoid system. The lymphatic system is a network of tissues, glands, and channels that produces lymphocytes, a type of white blood cell. Some lymphocytes remain in clusters within the lymph nodes, while others circulate throughout the body in the bloodstream or in the lymph, which is a clear yellowish fluid carried by the lymphatic channels. Lymphocytes fall into two groups: T cells, which regulate the immune system; and B cells, which produce antibodies. Burkitt's lymphoma involves the B-cell lymphocytes. In 1982, researchers discovered an oncogene (a gene that can release cells from growth constraints, possibly converting them into tumors) in 90% of patients with Burkitt's Lymphoma. Called the C-myc oncogene, it is responsible for the uncontrolled production of B-lymphocytes. It results from a translocation, or exchange, of genetic material between the long arm of human chromosome 8 and the long arm of human chromosome 14. In a smaller number of patients with Burkitt's Lymphoma, the translocation involves chromosomes 2 and 22 or chromosomes 2 and 8.

In the summer of 2000, researchers reported that a gene called the HMG-I/Y gene is also involved in the development of Burkitt's Lymphoma. The C-myc on-cogene appears to stimulate the HMG-I/Y gene, which then triggers the changes in normal B cells that cause them to multiply rapidly and form tumors.

Causes – Viruses:
In addition to translocations of genetic material, Burkitt's Lymphoma is also associated with oncogenic viruses—the Epstein-Barr virus (EBV) in Endemic Burkitt's and human immunodeficiency virus (HIV) in the Sporadic form. EBV, or human herpesvirus 4, is the virus that causes infectious mononucleosis. The presence of EBV in patients with Endemic Burkitt's has been interpreted as a side effect of the high rates of malaria in central Africa. African children may have immune systems that cannot fight off infection with EBV because they have been weakened by malaria. The children's B-lymphocytes then reproduce at an unusually high rate. Currently, however, the precise role of EBV in Burkitt's lymphoma is still being investigated, because the virus is less common in patients outside Africa. In the United States, about 25% of children and 40% of adult AIDS patients with Burkitt's have the Epstein-Barr virus.

Symptoms
In children, symptoms may appear as soon as four to six weeks after the lymphoma begins to grow. The more common symptom pattern is a large tumor in the child's abdomen accompanied by fluid buildup, pain, and vomiting. If the lymphoma begins in the blood marrow, the child may bleed easily and become anemic.

Diagnosis:
Burkitt's Lymphoma is usually diagnosed by examining a piece of tissue from a surgical biopsy of a swollen area in the patient's body—often the abdomen in the Sporadic form. The tissue is examined under a microscope by a pathologist, who is a physician with special training in the study of tissue or body fluid samples. In Burkitt's Lymphoma, the tumor cells will show a very high rate of cell division and a characteristic "starry sky" pattern. The pathologist may also test the tissue sample for the presence of EBV, which is found in about 30% of patients diagnosed with Burkitt's Lymphoma in the United States.

In addition to a tissue biopsy, the patient is also given a complete blood count (CBC) test, a platelet count, and a lumbar puncture (spinal tap). A small sample of bone marrow is usually taken as well. Most cases of Burkitt's Lymphoma do not require extensive x rays, although CT (computed tomography) scans of the chest and abdomen are usually taken, as well as a gallium scan. This scan involves being injected with the radioactive isotope gallium, which is attracted to cancerous cells. Thus, when technicians scan images the body, they are able to pinpoint those cells.

Staging
The most common system of staging for non-Hodgkin's lymphomas (NHL’s) in adults, including Burkitt's Lymphoma, is the Ann Arbor system. It specifies four stages as follows:

• Stage I: The lymphoma is either limited to one group of lymph nodes either above or below the diaphragm, or is in an organ or part of the body other than the lymph nodes, but has not spread to other organs or lymph nodes.
• Stage II: The lymphoma is either in two or more lymph node groups on the same side of the diaphragm, or is in only one organ or site other than the lymph nodes but has spread to the lymph nodes near that organ or site.
• Stage III: The lymphoma is present in groups of lymph nodes on both sides of the diaphragm. It may involve an organ or site outside the lymph nodes, the spleen, or both.
• Stage IV: The lymphoma is disseminated (spread) throughout one or more organs outside the lymph nodes. There may or may not be involvement of lymph nodes that are remote from the affected organs.

At each stage, the patient's condition may be described in more detail by using letters to denote the presence of specific general symptoms and/or the body organs that have been affected by the disease. A is used to designate patients who do not have general symptoms; B is used for patients with any of the following:

• unexplained loss of more than 10% of body weight in the last six months
• unexplained fever higher than 38 degrees C (101 degrees F)
• drenching night sweats

The letter E is added if the patient has developed malignancies outside the lymph nodes in areas of the body other than the lymphatic system. Other sites in the body are identified with additional letters, such as D for the skin or H for the liver.

The most commonly used staging system for NHL in children is that of the St. Jude's Children's Research Hospital. It separates patients with a single tumor or diseased lymph node (Stage I) or two or more tumors or diseased lymph nodes on the same side of the diaphragm (Stage II) from those with a large chest or abdominal tumor (Stage III) or involvement of the bone marrow and central nervous system (Stage IV).

Treatment
Because of the rapid rate of tumor growth in this lymphoma, it is important to begin treatment as soon as possible after diagnosis. Bulky abdominal tumors or chest tumors are sometimes removed surgically before the patient begins chemotherapy.

Children with Burkitt's Lymphoma are treated with chemotherapy and (sometimes) radiation therapy. Radiation therapy is used to treat lymphomas that affect the jaw and the area around the eyes. Children with Sporadic Burkitt's Lymphoma are treated with a short course of high-dose chemotherapy, usually cyclophosphamide in combination with methotrexate (MTX), vincristine (Oncovin), prednisone (Meticorten), and doxorubicin (Adriamycin). To prevent the spread of the lymphoma to the central nervous system, the patient's head and spine may be treated with radiation therapy and intrathecal methotrexate. In intrathecal chemotherapy, the drug is injected directly into the patient's spinal fluid.

Newer methods of treatment include bone marrow or stem cell transplantation and monoclonal antibodies (antibodies produced by cloned mouse cells grown in a laboratory). One monoclonal antibody, rituximab (Rituxan), has been approved by the FDA for treatment of non-Hodgkin's lymphomas, including Burkitt's Lymphoma. Clinical trials in France indicate that rituximab combined with standard chemotherapy improves the rates of remission and survival in high-risk patients.

Prognosis
The prognosis for children with Burkitt's Lymphoma is generally good, as this type of lymphoma responds well to chemotherapy. In the United States, 80% of children treated for early-stage Burkitt's Lymphoma remain free from relapse three years after treatment. The newer CODOX-M/IVAC combination chemotherapy has been credited with a cure rate above 90% in both children and adults.

Alternative and Complementary Therapies
Alternative and complementary treatments that have been reported as helpful to lymphoma patients include yoga, therapeutic massage, meditation, creative visualization, acupuncture, Reiki, journaling, and art therapy.

Children
Children being treated for Burkitt's Lymphoma share many of the concerns of children with other types of cancer, such as changes in appearance (hair loss caused by chemotherapy), continuing a normal schedule (school, sports participation), and coping with such other side effects of treatment as nausea or fatigue. One useful resource is the Candlelighters programs, which offer support and practical information to the parents of children with cancer.

Prevention
Some risk factors associated with the Sporadic form can be lowered, most particularly lifestyle behaviors that increase the risk of HIV infection. In addition, patients with Burkitt's Lymphoma may want to consider genetic counseling because of the role of the C-myc oncogene in their disorder.

Special Concerns
Patients diagnosed with Burkitt's Lymphoma should be followed up at regular intervals after chemotherapy because of the possibility of long-term relapse. Follow-up examinations should include a general physical examination, a complete blood count, and radiologic examinations.

The following information has been extracted from the Children’s Hospital Boston website:

What is Burkitt's Lymphoma?

Burkitt's Lymphoma (also called small noncleaved cell lymphoma) is a type of non-Hodgkin's lymphoma, a cancer in the lymphatic system. The lymphatic system is part of the immune system, and functions to fight disease and infections.
The lymphatic system includes:

• lymph fluid - fluid containing lymphocyte cells.
• lymph vessels - thin tubes that carry lymph fluid throughout the body.
• lymphocytes - specific white blood cells that fight infections and disease. The two main types of lymphocytes are B-cells and T-cells. Normal B-cells mature into plasma cells and produce immunoglobulins (also called antibodies) that help protect the body from bacteria. Normal T-cells serve in several roles to help protect the body. They recognize and destroy virus-infected cells, and they help attract other white blood cells that kill infected cells. There are several types and different stages of maturation for these cells.
• lymph nodes - bean-shaped organs, found in the underarm, groin, neck, chest, and abdomen, that act as filters for the lymph fluid as it circulates through the body
• spleen - a small organ that produces lymphocytes, stores healthy blood cells, and filters out damaged blood cells, bacteria and cell waste
• thymus - a small gland, located in front of the heart that plays a vital role in the development of T-cells while a child is still in the womb. Although the size of the gland starts to decrease after young adulthood, it continues to serve as part of the immune system throughout life.
• bone marrow/stem cells - the bone marrow contains stem cells, cells that develop into red blood cells, platelets (clotting cells) and infection-fighting white blood cells, including lymphocytes. Stem cells are also found circulating throughout the body in the blood stream.

Non-Hodgkin's lymphoma causes the cells in the lymphatic system to abnormally reproduce, eventually causing tumors to grow. Non-Hodgkin's disease cells can also spread to other organs and tissues in the body. Non-Hodgkin's lymphoma is the third most common childhood cancer. It occurs most often in children between the ages of 7 and 11, but can occur at any age from infancy to adulthood. Non-Hodgkin's lymphoma affects males almost three times more often than females, and is more common among Caucasian children than among African-American children and children of other races. Staging and classification of non-Hodgkin's lymphoma is based on the extent of the disease and the specific cells involved.

There are several types of non-Hodgkin's lymphomas, classified by physicians based on the size and shape of the lymphoma cells under a microscope, and how the cells grow within the lymph nodes and beyond. The type identified as Burkitt's lymphoma has what are considered small cells that are noncleaved, meaning the have no folds or indentations when viewed under a microscope. There is also a type of small, noncleaved lymphoma that has a somewhat different appearance under the microscope that is called non-Burkitt's lymphoma, which usually occurs in adults. Burkitt's lymphoma usually develops in the abdomen and spreads to other organs, including the brain. Burkitt's lymphoma involves B-cells and is a rapidly growing cancer.

For more information on other types of lymphoma, see large cell lymphoma, lymphoblastic lymphoma, or cutaneous or skin lymphomas.

What causes Burkitt's lymphoma?

The specific cause of non-Hodgkin's lymphoma is unclear. It is possible that genetics and exposure to viral infections may increase the risk for developing this malignancy. Non-Hodgkin's lymphoma has also been linked to chemotherapy and radiation therapy. Non-Hodgkin's may be a second malignancy as a result of the treatment for certain cancers.

There has been much investigation into the association of the Epstein-Barr virus (EBV) that causes the mononucleosis infection; as well as the human immunodeficiency virus (HIV), which causes acquired immune deficiency syndrome (AIDS). Both of these infectious viruses have been linked to the development of Burkitt's lymphoma. The majority of Burkitt's lymphoma cases result from a chromosome rearrangement between chromosome #8 and #14, which causes genes to change positions, and function differently, promoting uncontrolled cell growth.
Other chromosome rearrangements have been seen in non-Hodgkin's lymphoma (all types) that is also thought to promote excessive cell growth. Children and adults with other hereditary abnormalities have an increased risk of developing non-Hodgkin's lymphoma, including patients with ataxia telangiectasia, X-linked lymphoproliferative disease, or the Wiskott-Aldrich syndrome.

How is non-Hodgkin's lymphoma staged?

Staging is the process of determining whether cancer has spread and, if so, how far. There are various staging symptoms that are used for non-Hodgkin's lymphoma. Always consult your child's physician for information on staging. One method of staging non-Hodgkin's lymphoma is the following:

• stage I - involves the tumor at one site, either nodal or elsewhere in the body.
• stage II - involves the tumor at two or more sites on the same side of the body.
• stage III - involves tumors in any number that occur on both sides of the body, but does not involve bone marrow or the central nervous system.
• stage IV - is any stage of tumor that also has bone marrow and/or central nervous system involvement. Stage IV is also subdivided depending on the amount of blasts (cancer cells) present in the bone marrow.
What are the symptoms of non-Hodgkin's lymphoma?

Most children have stage III or IV disease at the time of diagnosis because of the sudden onset of symptoms. The disease can progress quickly from a few days to a few weeks. A child can go from otherwise healthy to having multi-system involvement in a short time period.

Some children with non-Hodgkin's lymphoma have symptoms of an abdominal mass and have complaints of abdominal pain, fever, constipation, and decreased appetite - due to the pressure and obstruction a large tumor in this area can cause. Some children with non-Hodgkin's lymphoma have symptoms of a mass in their chest and have complaints of respiratory problems, pain with deep breaths (dyspnea), cough, and/or wheezing.

Because of the rapid onset of this malignancy, any respiratory symptoms can quickly worsen, causing a life-threatening emergency.

The following are the most common symptoms of non-Hodgkin's lymphoma. However, each child may experience the symptoms differently. Symptoms may include:

• painless swelling of the lymph nodes in neck, chest, abdomen, underarm, or groin
• fever
• sore throat
• fullness in groin area from node involvement
• bone and joint pain
• night sweats
• tiring easily (fatigue)
• weight loss/decreased appetite
• itching of the skin
• recurring infections
The symptoms of non-Hodgkin's lymphoma may resemble other blood disorders or medical problems. Always consult your child's physician for a diagnosis.

How is non-Hodgkin's lymphoma diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for non-Hodgkin's lymphoma may include:

• blood and urine tests
• x-rays of the chest - uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film
• computerized tomography scan of the abdomen, chest, and pelvis (also called a CT or CAT scan) - a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general x-rays.
• lymph node biopsy - a sample of tissue is removed from the lymph node and examined under a microscope
• lymphangiogram - an imaging study that can detect cancer cells or abnormalities in the lymphatic system and structures. It involves a dye being injected into the lymph system.
• bone marrow aspiration/biopsy (to detect cancer cells) - a procedure that involves a small amount of bone marrow fluid and tissue to be taken, usually from part of the hip bones, to further examine the number, size, and maturity of blood cells and/or abnormal cells
• lumbar puncture (to evaluate central nervous system disease for cancer cells) - a special needle is placed into the lower back, into the spinal canal. This is the area around the spinal cord. A small amount of cerebral spinal fluid (CSF) can be removed and sent for testing. CSF is the fluid that bathes the brain and spinal cord.


What are the treatments for Burkitt's lymphoma?

Specific treatment for Burkitt's lymphoma will be determined by your child's physician based on:

• your child's age, overall health, and medical history
• the extent of the disease
• your child's tolerance for specific medications, procedures, or therapies
• the expectations for the course of the disease
• your opinion or preference
Treatment may include (alone or in combination):

• Chemotherapy - a drug treatment that works by interfering with the cancer cell's ability to grow or reproduce. Different groups of drugs work in different ways to fight cancer cells and shrink tumors. Chemotherapy may be used alone for some types of cancer or in conjunction with other therapy such as radiation. Often, a combination of chemotherapy drugs is used to fight a specific cancer. Certain chemotherapy drugs may be given in a specific order depending on the type of cancer it is being used to treat. While chemotherapy can be quite effective in treating certain cancers, the agents do not differentiate normal healthy cells from cancer cells. Because of this, there can be many adverse side effects during treatment. Being able to anticipate these side effects can help the care team, parents, and child prepare, and, in some cases, prevent these symptoms from occurring, if possible.

Chemotherapy is systemic treatment, meaning it is introduced to the bloodstream and travels throughout the body to kill cancer cells. Chemotherapy can be given:
o as a pill to swallow
o as an injection into the muscle or fat tissue
o intravenously (directly to the bloodstream; also called IV)
o intrathecally - chemotherapy given directly into the spinal column with a needle

Because Burkitt's lymphoma grows so quickly, chemotherapy treatment may be intense and last 6-8 months. Treatment may include drugs given directly to central nervous system (CNS) through the blood stream or a small puncture in the spine to prevent cancerous cells from multiplying in the spinal cord or brain.
• Surgery - surgery usually plays a limited role in the treatment of lymphoma. In some instances, a child may need to have a tumor removed. This may be the case if, for example, the tumor originates in the mediastinum region, where it may compress the airway and/or the heart and major vessels. Surgery in this area may entail considerable risk, and must be carefully orchestrated between the surgeon, oncologist and anesthesiologist.
• Radiation therapy - using high-energy rays (radiation) from a specialized machine to damage or kill cancer cells and shrink tumors, if there is a bulky tumor involved.
• Stem cell transplant - a treatment involving stem cells, a specific type of cell from which all blood cells develop. Stem cells develop into red blood cells to carry oxygen, white blood cells to fight disease and infection, and platelets to aid in blood clotting. Stem cells are found primarily in the bone marrow, but some also circulate in the blood stream.

Treatment may begin with high-dose chemotherapy to destroy all of the bone marrow, stem cells and cancerous cells, in the body. Then, healthy stem cells collected from another individual whose tissue is the same as, or almost the same as, the patients are used. This is called allogeneic transplantation. This is the most common type of stem cell transplant used to treat lymphoblastic lymphoma. Often, stem cell transplant is most appropriate for patients who have recurrent or drug-resistant disease.

Sometimes, stem cells are collected from patients themselves prior to intensive treatment and used to supplement the recovery after a particularly aggressive course of treatment. Through this procedure, stem cells are taken from the patient, treated in a laboratory to kill any remaining cancer cells, and kept in frozen storage for later use. After chemotherapy and/or radiation therapy, the saved stem cells are thawed and given back to the patient to grow new bone marrow and other stem cells. The use of a patient's own cells is referred to as autologous transplantation.

• Antibiotics - to prevent or treat infections
• Supportive care - for side effects of treatment
• Long-term follow up care - to determine response to treatment, detect recurrent disease, and manage late effects of treatment
Long-term outlook for a child with non-Hodgkin's lymphoma:

Prognosis greatly depends on:

• the extent of the disease
• the presence or absence of metastasis
• the response to therapy
• age and overall health of the child
• your child's tolerance of specific medications, procedures, or therapies
• new developments in treatment

As with any cancer, prognosis and long-term survival can vary greatly from child to child. Every child is unique and treatment and prognosis is structured around the child. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential for the child diagnosed with non-Hodgkin's lymphoma. Side effects of treatment, as well as second malignancies, can occur in survivors of non-Hodgkin's lymphoma. New methods are continually being discovered to improve treatment and to decrease side effects.

What is the latest research on Burkitt's Lymphoma?

The Dana-Farber/Children Hospital program is part of the Children's Oncology Group, a national group of pediatric oncologists whose work includes investigational treatments for newly diagnosed patients with non-Hodgkin's lymphoma and those who experience relapse. Studies also seek to improve the supportive care of patients undergoing treatment.

One area of treatment under investigation is biological therapy or immunotherapy, the use of drugs that seem to slow the growth of cancer cells while stimulating and strengthening the body's own immune system. Improvements are also occurring in the area of stem cell transplant, including ways to improve pre-transplant treatment, broaden the range of compatible donors, and developing more effective ways of removing cancerous cells from patient's own bone marrow.