Burkitt's lymphoma

What is Burkitt's lymphoma?

Burkitt's lymphoma is a high-grade B-cell non-Hodgkin's lymphoma that is rapidly growing and aggressive.^{1 2} There are three main types of Burkitt's lymphoma:

• Endemic: mainly occurs in equatorial Africa. It is the most common malignancy of children in this area. Is associated with chronic malaria and Epstein-Barr virus (EBV).³ It particularly affects the jaw, other facial bone, distal ileum, caecum, ovaries, kidney or breast.

• Sporadic: occurs outside Africa. Also associated with EBV but to a lesser degree. Most often affects the ileocaecal region and the jaw is less often involved.

• Immunodeficiency-associated: usually associated with HIV infection or the use of immunosuppressive drugs.

The cells in endemic and sporadic forms are B lymphocytes that have rearranged immunoglobulin genes and contain one of three translocations of the proto-oncogene c-myc. The most common translocation is from the long arm of chromosome 8 to chromosome 14.⁴

See also the separate article on Non-Hodgkin's Lymphoma.

How common is Burkitt's lymphoma? (Epidemiology)^{4 5}

• It most commonly affects children but can occur in adults. In children (<18 years old) the incidence is 3-6 cases per 100,000 population annually with peak diagnosis at 6 years of age.

• Burkitt's and 'Burkitt-like' lymphomas account for 1-5% of all non-Hodgkins lymphomas.⁵

• It is more common in males than females in a ratio of 3-4:1.

• Burkitt's lymphoma is significantly more common in sub-Saharan Africa, where it accounts for approximately one half of childhood cancers.⁶ The incidence peaks at around 5-8 years of age and is more common in boys.⁷

• The incidence also appears to be higher in South America, North Africa and in the Middle East. It is also endemic in Papua New Guinea.

• The sporadic form is rare in the developed world.

• There is an association with EBV and the sporadic and endemic forms of Burkitt's lymphoma. This association is stronger for the endemic form but may still be implicated in about 20% of the sporadic form.

• Malaria has been recognised as an important cofactor in endemic Burkitt's lymphoma.

• Arboviral infection (transmitted by insect vectors) and tumour-promoting plant extract-derived herbal remedies have also been proposed as cofactors.

Symptoms of Burkitt's lymphoma (presentation)

Endemic Burkitt's lymphoma

• Most commonly involves the maxilla and/or mandible; however, abdominal organs may also be involved.

• A tumour can double in size in 18 hours.⁶

• Presentation is commonly with:
  

  • Swelling of the affected jaw/bones.

  • Rapidly enlarging, non-tender lymph nodes in the neck/jaw.

Sporadic Burkitt's lymphoma

• Usually involves the abdominal organs, most frequently the distal ileum, caecum or mesentery.

• Other abdominal and pelvic organs, glandular tissue (such as the thyroid and tonsils) and the facial bones may also be involved.⁸

• Presentation is commonly with:
  

  • Abdominal mass/swelling and ascites.

  • Abdominal pain.

  • Intestinal obstruction.

Other presentations

• B symptoms may be present with both forms of Burkitt's lymphoma and include:
  

  • Fever.

  • Weight loss.

  • Night sweats.

• HIV-related Burkitt's lymphoma tends to present in a similar way to the sporadic disease.⁴

Investigations

• Biopsy is needed for diagnosis.

• Bone marrow and cerebrospinal fluid examination are usually performed (bone marrow and central nervous system (CNS) are frequently involved).

• Cytology of any ascitic or pleural fluid should be carried out.

• CXR, CT and MRI scanning allow staging.

• Positron emission tomography (PET) imaging and minimal residual disease (MRD) technology (flow cytometry and polymerase chain reaction (PCR) for immunoglobulin gene rearrangements) have also been introduced into protocols for investigation and staging.⁹

Stages of Burkitt's lymphoma

The St Jude Modification of Ann Arbor staging is widely used for staging:⁹

• Stage 1:
  

  • Single extranodal tumour OR localised nodal lymphoma (excluding mediastinal or abdominal lymph nodes).

• Stage 2 - can be any of:
  

  • Single extranodal tumour with nearby lymph node involvement.

  • Two single extranodal tumours on the same side of the diaphragm (± nearby lymph node involvement).

  • Lymphoma originating in the stomach or bowel (± nearby lymph node involvement).

  • Lymphoma involving two or more areas of lymph nodes on the same side of the diaphragm.

• Stage 2R:
  

  • Lymphoma was in the abdominal area and was completely removed by surgery.

• Stage 3 - can be any of:
  

  • Two single extranodal tumours on opposite sides of the diaphragm.

  • Lymphoma originating in the lungs, chest or thymus.

  • Lymphoma involving the spinal cord.

  • Lymphoma originating in the abdomen and involving a large area.

  • Lymphoma involving two or more areas of lymph nodes on opposite sides of the diaphragm.

• Stage 3A:
  

  • Lymphoma is within the abdominal cavity and is not amenable to surgery.

• Stage 3B:
  

  • Lymphoma involving several abdominal organs.

• Stage 4:
  

  • Any of the above PLUS, at the time of diagnosis, the CNS and/or the bone marrow being involved.

Management of Burkitt's lymphoma

Burkitt's lymphoma is a fast-growing tumour but also very sensitive to chemotherapy. However, sporadic and immunodeficiency-associated Burkitt's lymphoma can be less sensitive than the endemic variant to chemotherapy.⁷

Different regimens have been used with varied success rates.¹⁰ The development of brief but very intensive chemotherapy has led to a very high cure rate in children with Burkitt's lymphoma. The use of these regimens in adults, often in combination with the monoclonal antibody rituximab, can also be very effective.^{11 12}

Chemotherapy

• Combination chemotherapy is the treatment of choice; drugs used include cyclophosphamide, vincristine, doxorubicin, methotrexate, ifosfamide, cytarabine and etoposide.^{8 12}

• Treatment regimes usually include CNS prophylaxis with intrathecal chemotherapy.

• Non-intensive chemotherapy with cyclophosphamide and methotrexate may be an alternative to intensive chemotherapy for the management of the stage I-III endemic Burkitt's lymphoma in developing countries.¹³

Monoclonal antibody treatment

• Rituximab is often given with chemotherapy and improves outcomes.^{8 12}

Other treatment

• There is a high risk of tumour lysis syndrome. Allopurinol should be started at diagnosis with hydration and alkalinisation and close monitoring of electrolytes. Renal dialysis may be needed.

• Bone marrow transplantation or stem cell transplants may be performed if Burkitt's lymphoma is recurrent or extensive. Regimes may include high-dose chemotherapy ± radiotherapy.⁸

• Surgery has been used if there is intestinal obstruction or if abdominal tumours are very small and completely resectable.

Complications of Burkitt's lymphoma

• Intestinal obstruction.

• Tumour lysis syndrome.

Prognosis

• This depends on the stage at diagnosis and presence of associated risk factors. If there is localised disease, the survival rate is very high (over 90%).

• Across clinical trials many people with Burkitt's lymphoma can be cured with intensive chemotherapy, achieving 5-year survival rates between 75-85%.¹²

• A prognostic index has been developed which can derive estimates of 3-year progression free survival based on risk factors and patient factors.¹⁵

• Prognosis is generally poor in people with CNS involvement, and also with co-existent AIDS as there is usually widespread dissemination at diagnosis.

• Rarely, Burkitt's lymphoma can undergo leukaemic transformation.⁷

Prevention of Burkitt's lymphoma

Possible future considerations include:⁶

• Vaccine development for EBV.

• Vaccine development for malaria.