CNS prophylaxis in diffuse large B-cell lymphoma: if, when, how and for whom?

Area of Science:

• Hematology
• Oncology
• Neurology

Background:

• Central nervous system (CNS) relapse is a rare but severe complication of diffuse large B-cell lymphoma (DLBCL).
• The pathophysiology of CNS relapse in DLBCL is not well understood, leading to variable chemoprophylaxis practices.
• Current prophylactic strategies are often based on models from childhood leukemia, which may not be applicable to DLBCL.

Purpose of the Study:

• To critically review the literature on CNS relapse in DLBCL.
• To address the ineffectiveness of current chemoprophylaxis paradigms.
• To propose future research directions for CNS involvement in DLBCL.

Main Methods:

• Literature review and critical appraisal of existing studies on CNS relapse in DLBCL.
• Analysis of the differences in CNS involvement patterns between DLBCL and childhood leukemia.
• Evaluation of the evidence supporting current chemoprophylaxis strategies.

Main Results:

• Intrathecal prophylaxis is largely ineffective for DLBCL CNS involvement, which primarily affects brain parenchyma (approx. 60% of cases).
• CNS relapse in DLBCL may stem from occult malignant cells at diagnosis or later acquisition of CNS-penetrating clones.
• There is a lack of evidence to support the benefit of current chemoprophylaxis for preventing CNS relapse in DLBCL.

Conclusions:

• Current chemoprophylaxis for CNS relapse in DLBCL lacks strong evidence of benefit.
• The distinct patterns of CNS involvement in DLBCL necessitate different approaches compared to other hematologic malignancies.
• Prospective trials are crucial for advancing the understanding and treatment of CNS disease in DLBCL.