Treatment Outcome in Children With Central Nervous System-Positive Burkitt Lymphoma Using Only Intrathecal and Systemic Chemotherapy Combined With Rituximab

Burkitt lymphoma (BL) is the most common type of non-Hodgkin lymphoma in children, making up nearly 40% of pediatric cases. While standard chemotherapy now helps more than 90% of BL patients survive long-term, kids whose cancer has spread to the central nervous system (CNS)—the brain and spinal cord—face a much higher risk of poor outcomes. A 2021 study from Beijing Children’s Hospital offers hope: combining targeted therapy (rituximab) with specialized chemotherapy can significantly improve survival for these high-risk children.

What the Study Examined

The research team, led by Dr. Yong-Hong Zhang and colleagues from Beijing Children’s Hospital’s Haematology Oncology Center, analyzed data from 78 children diagnosed with CNS-positive (CNS+) BL between 2007 and 2019. All patients received a modified version of the international FAB/LMB96 chemotherapy regimen—designed specifically for B-cell lymphomas—plus rituximab (a monoclonal antibody that targets cancerous B-cells). Notably, no children received radiation therapy to the brain, which can cause long-term side effects in kids.

To be included, patients had to be newly diagnosed with CNS+ BL (defined by brain/spinal cord tumors, cranial nerve palsy, or cancer cells in cerebrospinal fluid [CSF]) and complete the hospital’s treatment plan. Fourteen patients were excluded (e.g., transferred from other hospitals, unable to finish chemo), leaving 78 for analysis.

Who Were the Patients?

Most kids (65 boys, 13 girls) were around 5.7 years old at diagnosis—typical for BL, which often strikes young children. Nearly half (48.7%) had bone marrow involvement, and more than half (56.4%) had intracerebral masses (ICMs, or tumors in the brain). Other common CNS symptoms included cranial nerve palsy (61.5%, weakness in face/eye muscles) and para-meningeal extension (32%, cancer spreading to tissues around the brain/spinal cord). About 19% had abnormal CSF (either by cell shape or immune markers).

How Were They Treated?

The regimen combined systemic chemotherapy (drugs given through veins to reach the whole body) and intrathecal chemotherapy (drugs delivered directly into the fluid around the spinal cord and brain—critical for targeting CNS cancer). Key drugs included methotrexate (high-dose to penetrate the blood-brain barrier) and rituximab (given 6 times at 375 mg/m²). To reduce dangerous side effects like tumor lysis syndrome (when dying cancer cells release toxins), kids with large tumors or high uric acid levels got urate oxidase.

What Were the Results?

After a median follow-up of 34 months (range: 1–72 months), the 3-year overall survival (OS) rate (percentage of kids alive 3 years after diagnosis) was 78.9% ± 4.7%. The 3-year event-free survival (EFS) rate (kids alive without relapse, progression, or death) was 71.4% ± 6.0%.

While these numbers are lower than survival rates for non-CNS+ BL, they represent a major improvement over older treatments. For example, past studies using simpler chemo regimens (like CHOP) saw 5-year EFS rates below 50% for CNS+ BL.

Key Risk Factors

The study identified three factors linked to worse outcomes:

Chemotherapy only: Kids who didn’t get rituximab had a 3-year EFS of just 33.3%, compared to 76.1% for those who got rituximab plus chemo.
Intracerebral mass (ICM): Kids with brain tumors had a 3-year EFS of 59.6%, versus 95.2% for those with para-meningeal extension (PME) and 75.5% for those with no CNS mass.
More than 4 organs involved: Kids whose cancer spread to 5+ organs had a 3-year EFS of 63.9%, compared to 91.3% for those with fewer than 4 organs affected.

Side Effects and Relapses

Five kids (6.4%) died from treatment-related infections—most in the early years of the study, when the team had less experience managing complications. Thirteen (16.7%) relapsed: 6 in the CNS, 6 in other parts of the body, and 1 with a late non-CNS relapse who achieved second remission. One child developed a second cancer (acute myeloid leukemia) 6 months after stopping treatment.

Why This Matters

CNS involvement is one of the strongest predictors of poor survival in BL. Before this study, most research on CNS+ BL focused on Western populations, where CNS involvement rates are lower (9%–13%) than in China (19% in this study). The Beijing team’s results show that a rituximab-boosted regimen—without brain radiation—can work for Chinese kids.

Rituximab was a game-changer: adding it to chemo nearly doubled EFS for kids who got both treatments. The team also adjusted methotrexate doses (total 29 g/m²) to balance effectiveness and side effects, reducing severe infections and mouth sores.

Limitations and Next Steps

As a retrospective study (looking back at medical records), the research can’t prove causality—only associations. The team also noted that early treatment complications (like infections) lowered survival rates, but experience has since reduced these issues.

The biggest takeaway? This regimen is a step forward, but more work is needed. The authors call for large, multicenter randomized trials to confirm the results and refine the treatment for Chinese kids.

Final Thoughts

For families of kids with CNS+ BL, this study offers hope: a targeted, radiation-free regimen can improve survival while minimizing long-term harm. As Dr. Zhang and colleagues note, “Rituximab combined with a modified LMB96 regimen has greatly improved the efficacy of treatment for Chinese children with CNS+ BL.”

The original study was published in the Chinese Medical Journal in 2021.

doi:10.1097/CM9.0000000000001386

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