Implications of the blood–brain barrier in primary central nervous system lymphoma

Abstract

<jats:p>✓ The optimal treatment of primary central nervous system lymphoma (PCNSL), a rare form of extranodal non-Hodgkin lymphoma, has yet to be defined. Whole-brain radiation therapy (WBRT) has limited efficacy as a single therapeutic modality and is associated with a high risk of delayed neurotoxicity. Methotrexate-based chemotherapy regimens yield poor drug penetration across the blood–brain barrier (BBB), thus necessitating administration of high doses with the concomitant risk of increased systemic and neurological toxicity. Combined-modality therapy (WBRT plus chemotherapy) can improve response and survival rates, yet it is associated with a high risk of neurotoxicity. The aim of chemotherapy in conjunction with BBB disruption is to maximize drug delivery to the brain and improve the agent's efficacy, while preserving neurocognitive function and minimizing systemic toxicity. Methotrexate-based chemotherapy regimens administered in conjunction with BBB disruption have shown promising results in PCNSL. Animal models of central nervous system lymphoma and drug neurotoxicity offer new possibilities to study the effects of various treatments on PCNSL and normal brain and can also help understand biological and pathophysiological aspects of this disease. Because the intact BBB is even less permeable to antibodies than it is to drugs, preclinical and clinical studies of monoclonal antibody delivery (for example, rituximab and <jats:sup>90</jats:sup>Y ibritumomab tiuxetan) to the brain in conjunction with BBB disruption offer a new possibility to make these novel treatments more efficient against PCNSL. Regarding the evaluation of more sensitive and specific diagnostic imaging tools, iron oxide–based contrast agents for magnetic resonance imaging have shown promise for better differentiation of PCNSL from other white matter diseases.</jats:p>

Brain parenchyma involvement as isolated central nervous system relapse of systemic non-Hodgkin lymphoma: an International Primary CNS Lymphoma Collaborative Group report

“…29 CNS-directed therapy, such as enhanced chemotherapy delivery with BBBD, may improve disease response and survival by increasing drug delivery to the CNS. 26,30 In our series, 8 of 31 patients who survived more than 2.5 years received either methotrexate (intravenously) followed by consolidation with highdose chemotherapy and peripheral blood stem cell transplantation; or methotrexate (intraarterially or intravenously) in conjunction with osmotic BBBD, as treatment for brain relapse (Table 7).…”

Image-Guided Convection-Enhanced Delivery Platform in the Treatment of Neurological Diseases

“…5,6 This technology has been successful in the treatment of many neuro-oncologic conditions in a number of centers, 7 and especially with primary central nervous system (CNS) lymphoma. 8 Unfortunately, despite selective opening of unilateral or bilateral vertebrobasilar or carotid cerebrovascular distributions via the arterial approach, controlling the region of treatment through this technique remains complicated and limited to a major vascular distribution. In addition, repeated treatments add to patient discomfort and potential morbidity, ultimately narrowing the clinical use of osmotic BBB disruption therapy.…”

Invasive pulmonary Successful treatment of Epstein-Barr virus-related post-transplant lymphoproliferative disease with central nervous system involvement following allogeneic haematopoietic stem cell transplantation –a case study

“…Despite the known value of rituximab in the treatment of B-lymphomas and PTLD, in case of CNS involvement the problem of blood-brain barrier impermeability occurs as a factor limiting the effectiveness of this drug administered intravenously [16]. There are attempts to administer rituximab intrathecally [5, 17] to improve its efficacy in the CNS; however, such treatment has not been licensed so far.…”