January 14, 2007

Burkitt Lymphoma

Synonyms and related keywords: undifferentiated lymphoma, Burkitt type small noncleaved FCC, small noncleaved cell B-cell neoplasm


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.


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.



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.


Acute Lymphoblastic Leukemia
Wilms Tumor

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.


Lab Studies:

Imaging Studies:


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.


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.

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.


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 Name
Cyclophosphamide (Cytoxan, Neosar) -- Nitrogen mustard derivative. Biotransformed by cytochrome P-450 system to hydroxylated intermediates that break down to active phosphoramide mustard and acrolein. Interaction of phosphoramide mustard with DNA considered cytotoxic. Effective alone in susceptible cases, but frequently used concurrently or sequentially with other antineoplastics. Used in CHOP and COMP regimens.
Adult DoseCHOP
Induction: 750 mg/m2 IV on day 1 and day 22
Consolidation: 750 mg/m2 IV on day 1
Induction: 1200 mg/m2 IV on day 1
Maintenance: 1000 mg/m2 IV on day 1 of wk 1, 4, and 8
Intensive 5-drug protocol from Stanford: 1200 mg/m2 IV on day 1 of each cycle
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; severely depressed bone marrow function
InteractionsAllopurinol may increase risk of bleeding or infection and exacerbate myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Pregnancy D - Unsafe in pregnancy
PrecautionsMany conditions (ie, leukopenia, thrombocytopenia, tumor cell infiltration of bone marrow, previous radiation therapy, previous therapy with other cytotoxic agents, impaired hepatic or renal function) increase risk of toxicity; regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; advise women to discontinue breastfeeding because of potential for serious adverse reactions or tumorigenicity
Drug Name
Doxorubicin (Adriamycin, Rubex) -- Cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius. Blocks DNA and RNA synthesis by inserting between adjacent base pairs and binding to sugar-phosphate backbone of DNA. Also generates oxygen radicals through lipid peroxidation, causing DNA strand breaks.
Adult DoseCHOP
Induction: 50 mg/m2 IV on day 1 and day 22
Consolidation: 50 mg/m2 IV on day 1
Intensive 5-drug protocol from Stanford: 40 mg/m2 IV on day 1 of each cycle
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function; marked myelosuppression induced by antitumor agents or by radiation therapy; previous treatment with complete cumulative doses of doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenes
InteractionsPaclitaxel may decrease clearance and increase toxicity (ie, more profound neutropenic and stomatitis episodes); progesterone may increase toxicity (ie, neutropenia, thrombocytopenia); cyclophosphamide, verapamil can increase cardiac toxicity; cyclosporine enhances hematologic toxicity, induces coma or seizures; phenobarbital increases elimination; digoxin and phenytoin levels may be decreased; streptozocin may inhibit hepatic metabolism; administration of live vaccines to immunosuppressed patients may be hazardous; mercaptopurine increases toxicity
Pregnancy D - Unsafe in pregnancy
PrecautionsIrreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in impaired hepatic function; advise patient that therapy imparts red coloration to urine for 1-2 d; observe during initial treatment and periodically monitor CBC count, LFT, and LVEF; advise women to discontinue breastfeeding
Drug Name
Vincristine (Oncovin) -- Vinca alkaloid extracted from periwinkle plant. Inhibits microtubule formation in mitotic spindle fibers, resulting in cell cycle arrest in metaphase. Used in CHOP and COMP regimens.
Adult DoseCHOP
Induction: 1.5 mg/m2 IV every wk for 6 wk
Consolidation: 1.5 mg/m2 IV on day 1
Induction: 2.0 mg/m2 IV every wk for 4 wk
Maintenance: 1.5 mg/m2 IV every wk for 6 wk
Intensive 5-drug protocol from Stanford: 1.4
mg/m2 IV on day 1 of each cycle
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity
InteractionsDecreases phenytoin levels; itraconazole increases neurotoxicity; nifedipine increases elimination half-life; drugs affecting CYP3A4 may alter metabolism, serum level, toxicity, or effectiveness; mitomycin-C may induce acute pulmonary reaction
Pregnancy D - Unsafe in pregnancy
PrecautionsIT administration fatal
Caution in patients diagnosed with severe cardiopulmonary or hepatic impairment and patients with preexisting neuromuscular disease; avoid in demyelinating form Charcot-Marie-Tooth syndrome; may induce tumor lysis syndrome—monitor serum uric acid; vesicant—avoid extravasation
Drug Name
Methotrexate (Folex PFS, Rheumatrex) -- Antimetabolite effective in treating some neoplasms (eg, Burkitt lymphoma), severe psoriasis, and adult rheumatoid arthritis. Used in COMP and CHOP regimens. May be used IT. Leucovorin rescue included in some regimens.
Adult DoseSystemic therapy
COMP: 300 mg/m2 IV for induction in end of wk 2 and maintenance in beginning of wk 3, 7, and 11
CHOP: 25 mg/m2 PO weekly for maintenance
Intensive 5-drug protocol from Stanford: 3 g/m2 IV on day 10 and q21d
IT therapy
COMP: 12 mg/m2 IT on days 0 and 14 of induction and on day 0 of each maintenance course CHOP regimen, 12 mg/m2 IT on days 1, 8, and 22 of induction, day 1 of consolidation and every 6 wk during maintenance therapy
Intensive 5-drug protocol from Stanford: 12 mg/m2 IT on days 1 and 10 of cycles 2-4; administer at onset of methotrexate infusion
Pediatric DoseIT therapy:
1 year: 8 mg
2 years: 10 mg
3-8 years: 12 mg
>9 years: 15 mg
ContraindicationsDocumented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
InteractionsCoadministration with NSAIDs may be fatal
Oral aminoglycosides, tetracycline, or chloramphenicol may decrease absorption and blood levels; charcoal lowers levels; etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; indomethacin and phenylbutazone can increase plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMX, may increase effects and toxicity; may increase plasma levels of thiopurines; cisplatin may increase nephrotoxic effects; penicillins may reduce renal clearance; may decrease clearance of theophylline
Pregnancy X - Contraindicated in pregnancy
PrecautionsMonitor CBC counts monthly, and liver and renal functions every 1-3 mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration, impaired renal function, ascites, pleural effusions); has toxic effects on hematologic, renal, GI, pulmonary, and neurological systems; discontinue if significant drop in blood counts, diarrhea, or ulcerative stomatitis occurs; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly, although possibility of increased toxicity with NSAIDs including salicylates has not been tested; potentially fatal opportunistic infections (ie, Pneumocystis carinii pneumonia) may occur; associated with development of malignant lymphomas, tumor lysis syndrome, or potentially fatal skin reactions; extreme caution in debilitated patients, breastfeeding women, and women of childbearing potential; folate deficiency may increase toxicity
Drug Category: Glucocorticoids -- The pharmacological properties of these agents are therapeutically effective in various diseases, including neoplasms.
Drug Name
Prednisone (Deltasone, Orasone, Meticorten) -- Glucocorticosteroid suppresses immune response, decreases inflammation, stimulates bone marrow, and influences protein, fat, and carbohydrate metabolism. Used in COMP and CHOP regimens. Large doses may require administration of gastroprotectant to prevent peptic ulcer.
Adult DoseCHOP: 40 mg/m2 PO qd for 28 d of induction and for 5 d of consolidation
COMP: 60 mg/m2 PO qd for 28 d of induction and for 7 d in wk 5 and 9 of maintenance
Intensive 5-drug protocol from Stanford: 40 mg/m2 PO qd on d 1-5
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
InteractionsEstrogens may decrease clearance; may cause digitalis (ie, digoxin) toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics; aspirin, NSAIDs (eg, indomethacin) increase risk of GI distress and bleeding; may cause altered response to oral anticoagulants; decreases response to skin-test antigens; toxoids and vaccines antibody response decreased and increased risk of neurological complications
Pregnancy B - Usually safe but benefits must outweigh the risks.
PrecautionsAvoid administration of live virus vaccines; abrupt discontinuation of glucocorticoids may cause adrenal crisis; caution in nonspecific ulcerative colitis, diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer; use associated with elevated BP, hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections; motility and number of spermatozoa may increase or decrease; prolonged use may cause posterior subcapsular cataracts or glaucoma with optic nerve damage; may activate latent amebiasis; may exacerbate strongyloides infection


Further Inpatient Care:

  • 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.


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


  • 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.


  • 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.

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