Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study

Haematologica. 2021 Jul 1;106(7):1932-1942. doi: 10.3324/haematol.2020.270876.


Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR], 1.53, 95% confidence interval [CI], 1.14-2.06, P=0.004) and overall survival (aHR, 1.62, 95%CI, 1.18-2.22, P=0.003). The 3-year cumulative incidence of CNS recurrence was 6% (95%CI, 4-8%). It was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-HR, 4.38, 95%CI, 2.16-8.87, P<0.001). Baseline CNS involvement in BL is relatively common and portends inferior prognosis independent of first-line regimen selection. In real-world practice, regimens with highly CNS-penetrant intravenous systemic agents were associated with a lower risk of CNS recurrence. This finding may be influenced by observed suboptimal adherence to the strict CNS staging and intrathecal therapy procedures incorporated in DA-EPOCH-R.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Burkitt Lymphoma* / diagnosis
  • Burkitt Lymphoma* / drug therapy
  • Burkitt Lymphoma* / epidemiology
  • Central Nervous System
  • Central Nervous System Neoplasms* / diagnosis
  • Central Nervous System Neoplasms* / drug therapy
  • Central Nervous System Neoplasms* / epidemiology
  • Cohort Studies
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Doxorubicin / therapeutic use
  • HIV Infections*
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Rituximab / therapeutic use
  • Young Adult


  • Rituximab
  • Doxorubicin
  • Cyclophosphamide

Grant support

Funding: This work was conducted with voluntary support of the contributing institutions and researchers, without any external funding.