What is the recommended treatment for Burkitt lymphoma?

Treatment of Burkitt Lymphoma

Burkitt lymphoma requires intensive, short-course, multi-agent chemotherapy regimens with aggressive CNS prophylaxis, and rituximab should be added for all CD20-positive tumors (which represents 86-100% of cases). 1, 2, 3

Diagnostic Requirements

Before initiating treatment, proper diagnosis is essential:

• Excisional lymph node biopsy providing adequate tissue for immunohistochemistry is mandatory 1
• Core needle biopsy alone is generally insufficient, though may be acceptable in emergency situations requiring immediate treatment 1
• Immunophenotyping must confirm: CD20+, CD10+, sIg+, TdT-, Ki-67+ (approaching 100%), BCL2-, BCL6+, with MYC rearrangement detected by cytogenetics or FISH showing t(8;14) or variants 1

Essential Staging Workup

Complete staging must be performed before treatment initiation:

• CT chest/abdomen/pelvis with contrast of diagnostic quality 1
• Lumbar puncture with cerebrospinal fluid analysis and prophylactic intrathecal chemotherapy (methotrexate and/or cytarabine) at the time of diagnostic tap 1, 2
• Bilateral bone marrow biopsy ± aspirate 1
• Laboratory evaluation: CBC with differential, comprehensive metabolic panel, LDH, uric acid, HIV testing, hepatitis B testing 1
• MUGA scan or echocardiogram if anthracycline-containing regimens are planned 1
• Pregnancy testing in women of childbearing age 1

Standard Treatment Regimens

CHOP chemotherapy is explicitly NOT adequate therapy for Burkitt lymphoma. 1 The following intensive regimens are recommended:

Low-Risk Disease

Choose one of the following regimens 1:

• CODOX-M (cyclophosphamide, doxorubicin, vincristine, high-dose methotrexate with intrathecal methotrexate and cytarabine) ± rituximab (3 cycles) 1, 4
• Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) with rituximab 1
• LMB protocol (pediatric-based regimen adapted for adults) 1
• CALGB 9251 regimen (cyclophosphamide-based with high-dose methotrexate, ifosfamide, cytarabine, and intrathecal triple therapy) 1

High-Risk Disease (CNS involvement, bone marrow involvement, Stage IV)

More intensive therapy is required 1, 2:

• CODOX-M/IVAC alternating regimen (CODOX-M alternating with ifosfamide, etoposide, cytarabine, intrathecal methotrexate) plus rituximab 1, 4, 5
• Modified LMB protocol with intensified CNS prophylaxis 1

Rituximab Integration

Rituximab must be added to chemotherapy for all CD20-positive Burkitt lymphoma (FDA-approved indication for pediatric patients ≥6 months with advanced stage disease and applicable to adults) 3, 2:

• Improves event-free survival by approximately 20% 2
• Standard dosing integrated with chemotherapy cycles 1, 6
• Has become standard of care even in immunodeficiency-related Burkitt lymphoma 6

CNS Prophylaxis (Mandatory for All Patients)

Systemic chemotherapy with intrathecal therapy is essential given the 20-30% lifetime risk of CNS involvement 2, 7:

• High-dose systemic methotrexate (significantly improves survival outcomes) 4
• Intrathecal chemotherapy (methotrexate and/or cytarabine) administered with each cycle 1, 7
• Particularly critical in high-risk patients with bone marrow involvement, testicular involvement, or involvement of spine/skull base 1

Critical Management Considerations

Tumor Lysis Syndrome Prevention

Given the extremely high proliferation rate (Ki-67 approaching 100%), aggressive prophylaxis is mandatory before and during initial chemotherapy 1, 7:

• Vigorous IV hydration 7
• Allopurinol or rasburicase (recombinant urate oxidase preferred for rapid uric acid reduction) 7
• Close monitoring of electrolytes, renal function, uric acid 1
• Consider prephase cytoreduction with corticosteroids and cyclophosphamide before full-dose chemotherapy in patients with high tumor burden 1

Treatment Intensity

Dose reductions should be avoided as they compromise cure rates 1:

• Prophylactic growth factor support (G-CSF) should be used to maintain dose intensity 1
• Treatment completion per protocol significantly improves outcomes (5-year PFS 86% vs lower rates with modifications) 4

Age-Related Outcomes

Younger patients (<40 years, particularly <60 years) have significantly better outcomes 2, 4:

• Age <60 years: 5-year PFS 82%, OS 86% 4
• This should inform treatment intensity decisions and counseling 2

Treatment Setting

Treatment should occur at centers with expertise in managing this complex, curable disease given the intensive nature of therapy and risk of life-threatening complications 1

Response Evaluation

• Restaging after 2-4 cycles and at completion of therapy with CT imaging 1
• PET-CT may be used for response assessment if available 1
• Repeat bone marrow biopsy and lumbar puncture only if initially involved 1

Relapsed/Refractory Disease

Prognosis is very poor for relapsed disease 6:

• High-dose chemotherapy with autologous stem cell transplant may be considered, though benefit remains uncertain 6
• Allogeneic stem cell transplant can be considered in selected cases 6
• Stem cell transplant in first remission has no proven benefit and should not be performed 4