AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Burkitt lymphoma is named after Denis Parsons Burkitt, who mapped its peculiar geographic distribution across Africa. It is a high-grade B-cell neoplasm and has 2 major forms, the endemic (African) form and the nonendemic (sporadic) form. Burkitt lymphoma is a childhood tumor but it is observed in adult patients. Burkitt lymphoma is one of the fastest growing malignancies in humans, with a very high growth fraction.

Pathophysiology

Burkitt lymphoma is a monoclonal proliferation of B lymphocytes characterized by small noncleaved cells that are uniform in appearance and that produce a diffuse pattern of tissue involvement. Under the microscope, Burkitt lymphoma is characterized by the presence of a "starry sky" appearance (also observed in other highly proliferative lymphomas), imparted by scattered macrophages with phagocytes cell debris.

The African form most often involves the maxilla or mandible. The involvement of abdominal organs, such as the kidneys, ovaries, or retroperitoneal structures, is slightly less common. In contrast, the sporadic form usually involves abdominal organs, with the most common involvement of the distal ileum, cecum, or mesentery and less common involvement of other abdominal organs, pelvic organs, and facial bones.

Most Burkitt lymphomas carry a translocation of the c-myc oncogene from chromosome 8 to either the immunoglobulin (Ig) heavy-chain region on chromosome 14 [t(8;14)] or one of the light-chain loci on chromosome 2 (kappa light chain) [t(8;2)] or chromosome 22 (lambda light chain) [t(8;22)].

The Epstein-Barr virus (EBV) has been implicated strongly in the African form, while the relationship is less clear in the sporadic form. EBV is associated with about 20% of sporadic cases. Rare adult cases are associated with immunodeficiency, particularly AIDS. The lymphocytes have receptors for EBV and are its specific target. In the African form, the hosts are believed to be unable to mount an appropriate immune response to primary EBV infection, possibly because of coexistent malaria or another infection that is immunosuppressive. Months to years later, excessive B cell proliferation occurs.

Frequency

United States

Burkitt lymphoma is a very rare form of cancer in the United States, with about 100 new cases occurring each year.

International

Burkitt lymphoma is endemic in certain regions of equatorial Africa and other tropical locations between latitudes 10° south and 10° north. Incidence in these areas of endemic disease is 100 per million children.

Mortality/Morbidity

Before aggressive therapeutic programs, children with Burkitt lymphoma died rapidly. With combination chemotherapy and CNS prophylaxis, the survival rate is now at least 60%. Patients with limited disease have a survival rate of 90%. Patients with bone marrow and CNS involvement have a poor prognosis. Adults with the disease, especially those in the advanced stage, do more poorly than affected children.

Race

Burkitt lymphoma is endemic in people living in central Africa. It is sporadic in residents of the United States.

Sex

The male-to-female ratio is 2-3:1.

Age

Burkitt lymphoma is most common in children. In Africa, the mean age is 7 years. Outside Africa, the mean age is 11 years.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

• In the African form of Burkitt lymphoma, patients most often present with swelling of the affected jaw or other facial bones, loosening of the teeth, and swelling of the lymph nodes, which are nontender and rapidly growing, in the neck or below the jaw. Abdominal presentation is slightly less common.
• Patients with the sporadic form of Burkitt lymphoma most commonly present with abdominal tumors causing swelling and pain in the affected area. Some patients present with symptoms of bowel obstruction secondary to an ileal-cecal intussusception caused by tumor growth.
• Because of the rapid growth of the Burkitt tumor, patients may quickly manifest significant metabolic derangement and renal function impairment.
• Less common presentations of Burkitt lymphoma include an epidural mass, skin nodules, CNS symptoms, and bone marrow involvement.
• Rare cases of Burkitt lymphoma can present as acute leukemia (L3-ALL) with fever, anemia, bleeding, and adenopathy.

Physical

Major signs of Burkitt lymphoma include a soft tissue mass associated with the involvement of the jaw or other facial bones, enlarged cervical lymph nodes, abdominal masses, and ascites.

Causes

The exact cause and mechanisms of Burkitt lymphoma are not known.

• EBV is closely associated with the African form of Burkitt lymphoma. Some have postulated that, because of immunosuppression caused by coexistent malaria or another infection, the host is unable to generate an adequate T-lymphocyte response (ie, EBV-specific cytotoxic T cells) against B cells that are infected latently with EBV. This subsequently results in excessive B cell proliferation.
• In about 90% of cases of Burkitt lymphoma, the proto-oncogene c-myc has been translocated from its normal position on chromosome 8 to a location close to the enhancers of the antibody heavy chain genes on chromosome 14. In all the other cases, c-myc has been translocated close to the antibody light chain genes on chromosome 2 or 22. In every case, c-myc is in a region of vigorous gene transcription. Overproduction of the c-myc product may change the lymphocytes into cancer cells.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

Burkitt lymphoma must be distinguished from other primary abdominal tumors in childhood, including Wilms tumor, neuroblastoma, and peripheral neuroectodermal tumor. In the bone marrow, it must be differentiated from B and T precursor and myeloid leukemias. In peripheral B-cell lymphomas, the major differential diagnosis is with diffuse large B-cell lymphoma.

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

• General laboratory studies should include complete blood cell (CBC) count with differentials, a platelet count, serum levels of sodium, potassium, calcium, phosphorus, magnesium, uric acid and creatinine, and liver function tests.
• Biopsy of suspected lymph nodes or other disease sites, including bone marrow, is essential for the diagnosis.
• Cerebrospinal fluid (CSF) also should be evaluated in all cases.
• Cytogenetic studies of peritoneal or pleural fluid, when appropriate, should be performed for diagnostic or staging purposes.
• The least invasive procedure should be used to establish the diagnosis. The staging workup must be expedited because Burkitt tumor grows rapidly, causing life-threatening complications.
• The most suggestive lymph nodes should be selected for excisional biopsy. Frozen sections and needle biopsies are discouraged. Aspiration of bone marrow or effusions may provide the diagnosis and avoid lymph node biopsy.

Imaging Studies

• Imaging studies should include routine chest x-ray, CT scan or MRI of the primary site, chest, and abdomen, and gallium scan. Bone scan may be needed if clinically indicated. In addition, positron emission tomography (PET) has been reported very useful in staging lymphomas and monitoring treatment response.
• • Chest x-ray is necessary to rule out lung metastasis and mediastinal involvement. Chest CT should be performed if chest x-ray is abnormal.
  • CT scan or MRI of the primary site is important for evaluation of the extent of the primary disease.
  • Abdominal CT scan is required to evaluate the extent of disease such as involvement of retroperitoneal and mesenteric lymph nodes, liver, kidneys, ovaries, and other structures.
  • Head or spinal CT scan or MRI is indicated if neurological signs and symptoms are present.
  • Bone scan and plain bone radiographs are needed for patients with symptoms of bone involvement.
  • Fluorine 18-2-fluorodeoxyglucose (FDG)-PET is an imaging modality using physiological tracer glucose, whose uptake and metabolism is increased in tumor cells. FDG-PET scanning has been reported to be an efficient, non-invasive method for staging and monitoring of both Hodgkin and non-Hodgkin lymphomas, including Burkitt lymphoma, and is even more accurate than CT scan in detecting lesions.

Procedures

• Bone marrow aspiration and biopsy should be performed for every patient with Burkitt lymphoma because the frequent presence of unexpected bone marrow involvement has important implications for treatment planning.
• Lumbar puncture is necessary for evaluation of CNS involvement.
• Paracentesis or thoracentesis is needed for cytogenetic studies if ascites or pleural effusion is present.

Histologic Findings

Lymph node involvement occurs. Burkitt cells are homogeneous in size and shape, with round to oval nuclei and slightly coarse chromatin, with multiple nucleoli, and with intensely basophilic vacuolated cytoplasm that contains neutral fat. Frequent mitotic figures usually are observed. A starry sky appearance is imparted by scattered macrophages with phagocyte cell debris.

Staging

Various staging systems have been proposed.

• The National Cancer Institute (NCI) system
• • A - Single solitary extra-abdominal site
  • AR - Intra-abdominal, more than 90% of tumor resected
  • B - Multiple extra-abdominal tumors
  • C - Intra-abdominal tumor
  • D -Intra-abdominal plus one or more extra-abdominal sites

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medical Care

Burkitt lymphoma is a very fast growing tumor. Systemic chemotherapy is the treatment of choice for this aggressive disease in all its stages. The overall survival rate of Burkitt lymphoma depends upon the stage of the disease at initial diagnosis. Patients with localized disease respond well to chemotherapy and have an excellent survival rate. Patients with disseminated disease respond less well to chemotherapy and have a less favorable survival rate. Cyclophosphamide therapy alone has been curative for 80% of children from Africa with localized (early stage) disease. However, combination chemotherapy has markedly improved treatment results, particularly in patients with extensive disease. Short-duration, intensive, alkylator-based multiagent regimens are necessary for patients with extranodal tumors and for all patients with the sporadic form of the disease. Of particular importance is the rapid administration of successive cycles to prevent tumor regrowth.

In AIDS patients with Burkitt lymphoma, the disease usually is advanced at diagnosis and tends to involve extranodal sites. Most of these patients present with wide dissemination and bone marrow involvement. Because of their underlying immune deficiency and leukopenia, most of these patients tolerate systemic chemotherapy poorly. Death usually occurs shortly after diagnosis.

• For patients with limited disease, including localized extra-abdominal or completely resected abdominal disease (NCI stages A and AR), a long-term survival rate greater than 90% can be achieved with combination chemotherapy.
• • Treatment options include the following:
    • COMP - Cyclophosphamide + vincristine (Oncovin) + methotrexate + prednisone
    • CHOP - A similar regimen using doxorubicin in place of methotrexate
    • CHOP plus methotrexate
    • NHL-BFM90 - Prednisone + dexamethasone + vincristine + doxorubicin + cyclophosphamide + ifosfamide + etoposide + cytarabine + methotrexate
    • French LMB-89 - High-dose cyclophosphamide + high-dose methotrexate/leucovorin + cytarabine + vincristine + prednisone + doxorubicin
    • CCG-5961 - Reduction in intensification of the French LMB-89 regimen
  • CNS prophylaxis using intrathecal methotrexate with or without cytarabine and hydrocortisone is included in most regimens, although it may not be necessary for patients with completely resected, small-volume abdominal disease.
  • Link et al demonstrated that a 9-week regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone plus intrathecal prophylaxis was as effective for early stage disease as a longer regimen that included a continuation phase with or without radiation. With this and similar regimens for limited disease, cure rates exceed 90% with minimal toxicity. Thus, less intensive therapy is under evaluation as a potentially effective way to avoid unnecessary toxicity for patients with early stage disease, while achieving similar cure rates obtained with more prolonged treatment.
• For patients with extensive disease, a long-term survival rate of 70-80% now can be achieved with intensive chemotherapy regimens.
  • Current treatment options include the following:
    • French LMB-89, Total B - St. Jude's: high-dose cyclophosphamide + high-dose methotrexate + cytarabine
    • NHL-BFM90
    • NCI-89-C-0041F - Cyclophosphamide + vincristine + doxorubicin + methotrexate, alternating with cytarabine, etoposide, and ifosfamide
• • Vanderbilt Medical Center also reported encouraging results for patients with poor-prognosis non-Hodgkin lymphoma, including Burkitt lymphoma, using a high-dose and brief-duration combination chemotherapy regimen comprising cyclophosphamide + etoposide + doxorubicin + vincristine + bleomycin + methotrexate with leucovorin rescue + prednisone.
  • Intrathecal methotrexate should be used in all patients with extensive disease.
• Patients with Burkitt lymphoma, especially those with extensive disease, have a high risk of tumor lysis syndrome even before chemotherapy is initiated because of the rapid tumor cell turnover. This emergent life-threatening clinical situation should be anticipated and addressed prior to starting treatment. Patients should receive prophylactic allopurinol and aggressive hydration with alkalinization starting as soon as Burkitt lymphoma is diagnosed. Electrolytes, especially potassium, calcium, and phosphorus, as well as uric acid and creatinine, should be monitored closely. Treatment should be performed at a facility where renal dialysis is available should it be necessary, particularly for patients with extensive disease.
• Treatment of recurrent Burkitt lymphoma is difficult. Bone marrow transplantation is the only hope of long-term survival for these patients.

Surgical Care

Employ surgery only for patients with small, completely resectable abdominal tumors or patients with obstruction who cannot begin chemotherapy immediately.

Consultations

Hematology/oncology consultation is needed.

Diet

No specific diet is required.

Activity

Activity is as tolerated.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Two regimens and their modifications are the fundamental treatment protocols for Burkitt lymphoma. Drugs used in CHOP or COMP regimens have been studied extensively.

Drug Category: Antineoplastic agents

These agents prevent development, maturation, or spread of neoplastic cells.

Drug Category: Glucocorticoids

The pharmacological properties of these agents are therapeutically effective in various diseases, including neoplasms.

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Further Inpatient Care

• Closely monitoring serum chemistries in patients with Burkitt lymphoma is critical, especially during chemotherapy, because of the high risk of tumor lysis syndrome and uric acid nephropathy. Prophylactic allopurinol and aggressive hydration with alkalinization should be administered (see Medications).
• Close monitoring of CBC count and serum levels of uric acid, potassium, calcium, phosphorus, magnesium, and creatinine is necessary. Liver functions also should be monitored.

Further Outpatient Care

• When patients with Burkitt lymphoma receive treatment in the clinic, close monitoring of WBC count, hemoglobin, platelet count, serum chemistry, and liver functions is needed.

In/Out Patient Meds

• Chemotherapy drugs (Medications) and supportive care treatment are provided.

Deterrence/Prevention

• Presently, no effective measure exists to prevent the disease.

Complications

• In the abdominal form of the disease, rapid tumor growth may result in obstruction.
• Because of the extremely fast growth rate, massive acute destruction of the tumor cells during initial chemotherapy may result in tumor lysis syndrome requiring renal dialysis.

Prognosis

• The prognosis in children correlates with the bulk of disease at the time of diagnosis. With appropriate management of the metabolic consequences of rapid cell turnover and with combination chemotherapy and CNS prophylaxis, the survival rate has been improved significantly.
• Patients with limited (A, AR) disease have an excellent prognosis, with a survival rate greater than 90%.
• Patients with more extensive disease, especially bone marrow and CNS involvement, have a worse prognosis, but long-term survival rates as high as 80% can be achieved with more aggressive chemotherapy regimens.
• Adults with Burkitt lymphoma, particularly those with advanced stage disease, do more poorly than children with the disease.

Patient Education

• Provide information and support about the disease and the adverse effects of the drugs used to treat the disease to patients and the family members.
• Emotional support is very helpful to patients with cancer. Educating the medical personnel directly involved in patient care and the family members about emotional support for the patient is very important.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

• Adde M, Shad A, Venzon D, et al. Additional chemotherapy agents improve treatment outcome for children and adults with advanced B-cell lymphomas. Semin Oncol. Apr 1998;25(2 Suppl 4):33-9; discussion 45-8. [Medline].
• Atra A, Imeson JD, Hobson R, et al. Improved outcome in children with advanced stage B-cell non-Hodgkin''s lymphoma (B-NHL): results of the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol. Br J Cancer. Apr 2000;82(8):1396-402. [Medline].
• Barrington SF, Carr R. Staging of Burkitt''s lymphoma and response to treatment monitored by PET scanning. Clin Oncol (R Coll Radiol). 1995;7(5):334-5. [Medline].
• Bernstein JI, Coleman CN, Strickler JG, et al. Combined modality therapy for adults with small noncleaved cell lymphoma (Burkitt''s and non-Burkitt''s types). J Clin Oncol. Jun 1986;4(6):847-58. [Medline].
• Buchmann I, Moog F, Schirrmeister H, Reske SN. Positron emission tomography for detection and staging of malignant lymphoma. Recent Results Cancer Res. 2000;156:78-89. [Medline].
• Casciato DA, Lowitz BB. Burkitt's lymphoma. In: Manual of Clinical Oncology. 3rd ed. Baltimore, Md:. Lippincott Williams & Wilkins;1995:382-383.
• Cohen LF, Balow JE, Magrath IT, et al. Acute tumor lysis syndrome. A review of 37 patients with Burkitt''s lymphoma. Am J Med. Apr 1980;68(4):486-91. [Medline].
• DeVita VT Jr, Hellman S, Rosenberg SA, et al. Small noncleaved cell, or Burkitt's, lymphoma. In: Cancer: Principles and Practice of Oncology. Vol 2. Baltimore, Md:. Lippincott Williams & Wilkins;1997:2157-2159.
• Link MP, Donaldson SS, Berard CW, et al. Results of treatment of childhood localized non-Hodgkin''s lymphoma with combination chemotherapy with or without radiotherapy. N Engl J Med. Apr 26 1990;322(17):1169-74. [Medline].
• Link MP, Shuster JJ, Donaldson SS, et al. Treatment of children and young adults with early-stage non-Hodgkin''s lymphoma. N Engl J Med. Oct 30 1997;337(18):1259-66. [Medline].
• Magrath I, Adde M, Shad A, et al. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. Mar 1996;14(3):925-34. [Medline].
• Magrath IT, Janus C, Edwards BK, et al. An effective therapy for both undifferentiated (including Burkitt''s) lymphomas and lymphoblastic lymphomas in children and young adults. Blood. May 1984;63(5):1102-11. [Medline].
• McMaster ML, Greer JP, Greco FA, et al. Effective treatment of small-noncleaved-cell lymphoma with high-intensity, brief-duration chemotherapy. J Clin Oncol. Jun 1991;9(6):941-6. [Medline].
• Meadows AT, Sposto R, Jenkin RD, et al. Similar efficacy of 6 and 18 months of therapy with four drugs (COMP) for localized non-Hodgkin''s lymphoma of children: a report from the Childrens Cancer Study Group. J Clin Oncol. Jan 1989;7(1):92-9. [Medline].
• Medical Economics Staff. Physicians' Desk Reference. 54th ed. Medical Economics Co;2000:859-61, 1423-7, 1631-3, 1805-6, 2408-10.
• Patte C, Michon J, Frappaz D, et al. Therapy of Burkitt and other B-cell acute lymphoblastic leukaemia and lymphoma: experience with the LMB protocols of the SFOP (French Paediatric Oncology Society) in children and adults. Baillieres Clin Haematol. Jun 1994;7(2):339-48. [Medline].
• Reiter A, Schrappe M, Tiemann M, et al. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: A report of the Berlin-Frankfurt-Munster Group Trial NHL-BFM 90. Blood. Nov 15 1999;94(10):3294-306. [Medline].
• Schwenn MR, Blattner SR, Lynch E, Weinstein HJ. HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt''s lymphoma and B-cell acute lymphoblastic leukemia. J Clin Oncol. Jan 1991;9(1):133-8. [Medline].
• Shad A, Magrath IT. Malignant non-Hodgkin's lymphomas in children. In: Principles and Practice of Pediatric Oncology. 3rd ed. Baltimore, Md:. Lippincott Williams & Wilkins;1997:545-588.
• Soussain C, Patte C, Ostronoff M, et al. Small noncleaved cell lymphoma and leukemia in adults. A retrospective study of 65 adults treated with the LMB pediatric protocols. Blood. Feb 1 1995;85(3):664-74. [Medline].
• Waits TM, Greco FA, Greer JP, et al. Effective therapy for poor-prognosis non-Hodgkin''s lymphoma with 8 weeks of high-dose-intensity combination chemotherapy. J Clin Oncol. May 1993;11(5):943-9. [Medline].
• Waits TM, Greco FA, Greer JP. Treatment of poor prognosis non-Hodgkin''s lymphoma with intensive, inpatient combination chemotherapy of brief duration: long-term followup. Leuk Lymphoma. Aug 1993;10(6):453-9. [Medline].
• Ziegler JL. Chemotherapy of Burkitt''s lymphoma. Cancer. Dec 1972;30(6):1534-40. [Medline].
• Ziegler JL, Bluming AZ, Fass L, Morrow RH Jr. Relapse patterns in Burkitt''s lymphoma. Cancer Res. Jun 1972;32(6):1267-72. [Medline].
• Ziegler JL, Magrath IT, Gerber P, Levine PH. Epstein-Barr virus and human malignancy. Ann Intern Med. Mar 1977;86(3):323-36. [Medline].

Article Last Updated: Dec 12, 2005