What is the treatment for Burkitt lymphoma?

Treatment of Burkitt Lymphoma

Burkitt lymphoma requires intensive, short-duration, multi-agent chemotherapy regimens with aggressive CNS prophylaxis, and CHOP alone is explicitly inadequate therapy. 1

Diagnostic Requirements Before Treatment

Essential workup components include: 1

• Hematopathology review with adequate tissue (excisional or incisional biopsy preferred; FNA alone is insufficient) 1
• Immunophenotyping showing typical pattern: CD20+, CD10+, Ki-67 near 100%, BCL2-, BCL6+, TdT- 1
• Cytogenetics or FISH demonstrating MYC rearrangement [t(8;14) or variants] 1
• Lumbar puncture with CSF analysis (essential, not optional) 1
• Bone marrow biopsy (unilateral or bilateral) 1
• HIV and Hepatitis B testing (mandatory before rituximab) 1, 2
• CT chest/abdomen/pelvis with contrast 1
• Baseline cardiac function (MUGA or echocardiogram) if anthracyclines planned 1

First-Line Treatment Regimens

The standard approach uses intensive combination chemotherapy with rituximab for CD20+ disease: 1, 2

Low-Risk Disease

Acceptable regimens include (in alphabetical order): 1

• CODOX-M/IVAC ± rituximab (3 cycles): cyclophosphamide, doxorubicin, vincristine with intrathecal methotrexate/cytarabine followed by high-dose systemic methotrexate, then IVAC (ifosfamide, etoposide, cytarabine) 1
• CALGB 9251 regimen: cyclophosphamide/prednisone followed by cycles with ifosfamide or cyclophosphamide, high-dose methotrexate, leucovorin, vincristine, dexamethasone, and doxorubicin/etoposide/cytarabine 1
• Dose-adjusted EPOCH ± rituximab: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin 1

Pediatric Patients

For children aged 6 months and older with Burkitt lymphoma, rituximab combined with chemotherapy is indicated: 2

• The LMB protocol is an acceptable alternative to CODOX-M or HyperCVAD, with rituximab added for CD20+ tumors 1
• Rituximab dosing for pediatric patients: initiate infusion at 0.5 mg/kg/hr (maximum 50 mg/hr), increasing by 0.5 mg/kg/hr every 30 minutes to maximum 400 mg/hr 2

Critical Treatment Principles

CHOP chemotherapy is explicitly not adequate therapy for Burkitt lymphoma 1—this is a common pitfall that must be avoided, as CHOP lacks the intensity and CNS penetration required for cure.

High-dose systemic methotrexate is a critical component that significantly affects survival outcomes 3, and incorporation of this agent showed significant impact on multivariate survival (OS HR 0.28, P=0.025) 3.

Rituximab Integration

Rituximab should be added to chemotherapy for all CD20+ Burkitt lymphoma: 1, 2, 4

• Standard adult dosing: 375 mg/m² IV with each chemotherapy cycle 2
• Rituximab-based short-course dose-intensive chemotherapy has become standard of care, even in immunodeficiency-related forms 4
• Mandatory HBV screening (HBsAg and anti-HBc) before rituximab initiation, with prophylactic antiviral therapy for positive patients 1, 2

CNS Prophylaxis

Aggressive CNS prophylaxis is mandatory and non-negotiable: 1

• Intrathecal chemotherapy (methotrexate, cytarabine, hydrocortisone triple therapy) 1
• High-dose systemic methotrexate with leucovorin rescue 1
• Age-based intrathecal dosing (not BSA-based): <1 year = 6 mg; 1 year = 8 mg; 2 years = 10 mg; ≥3 years = 12 mg 5

Supportive Care Requirements

Critical supportive measures include: 1

• Tumor lysis syndrome prophylaxis (aggressive hydration, allopurinol or rasburicase, electrolyte monitoring) given the extremely high proliferation rate 1, 4
• Prophylactic growth factors for febrile neutropenia 1
• Antiemetics and hydration during high-dose methotrexate 1
• Leucovorin rescue: 15 mg orally every 6 hours for 10 doses starting 24 hours after methotrexate infusion 5

Treatment Setting

This disease is complex and curative; treatment should occur at centers with expertise in managing Burkitt lymphoma 1—the rapid proliferation (Ki-67 near 100%) and potential for tumor lysis syndrome require immediate access to intensive supportive care.

Expected Outcomes

Real-world outcomes with CODOX-M/IVAC ± rituximab demonstrate: 3

• 5-year progression-free survival: 75% (95% CI: 63-83%) 3
• 5-year overall survival: 77% (95% CI: 66-85%) 3
• Patients completing protocol per protocol: 5-year PFS 86%, OS 92% 3
• Patients under 60 years: 5-year PFS 82%, OS 86% 3
• Zero treatment-related deaths in this cohort 3

Long-term survival of 40-80% is achievable with combination intensive chemotherapy 6, and continuous remissions can be obtained without additional myeloablative chemotherapy when using appropriate intensive regimens 7.

Relapsed/Refractory Disease

Relapsed or refractory Burkitt lymphoma has very poor prognosis: 4

• The benefit from autologous or allogeneic hematopoietic stem cell transplant remains uncertain 4
• Stem cell transplant in first remission showed no effect on OS or PFS in real-world analysis 3

Common Pitfalls to Avoid

• Never use CHOP alone—this is explicitly inadequate and will result in treatment failure 1
• Do not delay treatment to obtain PET-CT—initiation should not be postponed 1
• Do not reduce doses for hematological toxicity—maintain dose intensity as reductions compromise efficacy 1, 7
• Do not omit lumbar puncture—CNS evaluation and prophylaxis are essential components 1
• Do not forget HBV screening—reactivation can be fatal with rituximab therapy 1, 2