Burkitt Lymphoma (BL)

Burkitt lymphoma is a highly aggressive mature B-cell lymphoma that can occur in both children and adults.

Its characteristic genetic feature is a MYC rearrangement, most commonly t(8;14), with t(8;22) and t(2;8) occurring less often. These abnormalities lead to increased MYC activity and very rapid tumor cell proliferation.

BL is commonly described as endemic, sporadic, or immunodeficiency-associated. These forms differ in their geographic patterns and common sites of involvement, but their underlying pathology and treatment principles are broadly similar.

Epstein-Barr virus (EBV) is strongly associated with some cases, particularly endemic BL, but EBV is not the sole cause of the disease.

Burkitt lymphoma is not caused by a single known factor.

The central molecular abnormality is a rearrangement involving the MYC gene, which drives extremely rapid cell growth. EBV is also associated with a subset of cases.

Impaired immune function can increase risk, including HIV infection and long-term immunosuppression after organ transplantation.

For most patients with sporadic BL, no specific lifestyle or environmental cause can be identified.

BL grows rapidly, and symptoms often develop over a short period of time. The presentation depends on the sites involved.

Endemic BL commonly affects the jaw, facial bones, and other extranodal sites and may also involve the bone marrow or central nervous system.

Sporadic BL more often involves the abdomen, particularly the bowel and abdominal cavity, and may cause:

• An abdominal mass

• Abdominal pain or swelling

• Nausea and vomiting

• Changes in bowel habits

• Bowel obstruction or gastrointestinal bleeding

Other possible symptoms include enlarged lymph nodes, enlargement of the liver or spleen, fever, drenching night sweats, and unexplained weight loss.

Bone marrow involvement may cause anemia or low platelet counts, while central nervous system involvement can cause headaches, vomiting, cranial nerve problems, or other neurological symptoms.

Diagnosis of BL combines tissue biopsy, pathology and immunophenotyping, genetic testing, and staging studies.

A tissue biopsy is essential. Pathology typically shows a highly proliferative mature B-cell lymphoma, supported by immunophenotypic markers such as CD20, CD10, and BCL6. The Ki-67 proliferation index is usually very high.

Genetic testing focuses on identifying a MYC rearrangement, most commonly t(8;14), t(8;22), or t(2;8).

Blood tests often include a complete blood count, kidney and liver function tests, electrolytes, uric acid, and lactate dehydrogenase (LDH). LDH may be elevated, particularly in patients with a high tumor burden.

PET/CT or CT may be used to determine the extent of disease.

Bone marrow evaluation may be needed to determine whether the marrow is involved.

Because BL carries a risk of central nervous system involvement, some patients also undergo lumbar puncture and cerebrospinal fluid testing.

BL grows extremely quickly, so treatment usually needs to begin soon after diagnosis.

The main treatment is short-course, intensive multi-agent chemotherapy, selected according to age, stage, tumor burden, and central nervous system involvement. Rituximab is commonly added for CD20-positive BL.

Treatment regimens vary by age, risk group, and treatment center and may include strategies based on LMB, BFM, CODOX-M/IVAC, or DA-EPOCH-R.

Central nervous system prophylaxis is an important part of BL treatment. Many treatment protocols include intrathecal chemotherapy even when there is no confirmed CNS involvement.

Tumor Lysis Syndrome Prevention

Because BL grows rapidly and often responds quickly to treatment, tumor lysis syndrome (TLS) is an important risk before and shortly after therapy begins.

Patients may need intensive hydration, uric acid–lowering treatment, and close monitoring of electrolytes and kidney function.

Relapsed or Refractory BL

If BL returns or does not respond adequately to initial treatment, further treatment depends on prior therapy, timing of relapse, disease extent, and overall health.

Options may include salvage combination chemotherapy, rituximab, and hematopoietic stem cell transplantation.

CAR-T cell therapy and bispecific antibodies are also being used or studied in selected patients with relapsed or refractory mature B-cell lymphoma, particularly in pediatric and adolescent settings, but they are not routine first-line treatment for newly diagnosed BL.

Hematopoietic Stem Cell Transplantation

Stem cell transplantation is not a routine first-line treatment for newly diagnosed BL.

For selected patients with relapsed or refractory disease, autologous or allogeneic transplantation may be considered after an adequate response to salvage treatment.