Blood-brain barrier permeability in diffuse large B-Cell lymphoma: associations with established risk factors for CNS relapse

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Central nervous system (CNS) relapse is a serious complication of diffuse large B-Cell lymphoma (DLBCL), often associated with poor clinical outcomes. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables detection of subtle blood-brain barrier (BBB) leakage. We assessed BBB permeability, using the Patlak model, in 63 patients with DLBCL without CNS involvement and 11 healthy controls using DCE-MRI, and investigated associations with established risk factors for CNS relapse. Patients with high risk of CNS relapse (CNS-IPI ≥4) demonstrated near-significant increased BBB permeability in cortical gray matter (GM) compared with both low-risk patients (p = 0.053) and healthy controls (p = 0.02). BBB permeability in cortical GM and in cerebral white matter (WM) correlated positively with age (p < 0.001). After adjusting for age, patients with kidney and/or adrenal involvement exhibited significantly higher BBB permeability in cortical GM (p = 0.04). Furthermore, plasma albumin levels were inversely correlated with BBB permeability in both GM (p = 0.003) and WM (p = 0.005). These findings indicate that subclinical BBB dysfunction may contribute to CNS vulnerability in DLBCL, potentially predisposing patients to relapse even before CNS involvement occurs. The observed age-related increase in BBB permeability is consistent with previous reports and may represent an independent risk for CNS relapse. Collectively, these results suggest that BBB imaging could improve CNS risk stratification in DLBCL. Prospective studies are warranted to determine whether early BBB alterations can predict CNS relapse in individual patients.

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