The need for prophylactic treatment to the central nervous system in patients with aggressive non-Hodgkin’s lymphoma

Hawkey, Chris J.; Toghill, P J

doi:10.1136/pgmj.59.691.283

Cited by 6 publications

(1 citation statement)

References 19 publications

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“…This was hypothesized when two patients with systemic lymphoma in remission experienced CNS involvement while undergoing treatment with multidrug chemotherapy. 30 The BBB normally excludes ionized, water-soluble drugs with molecular weights greater than 180 D from entering the brain, and most chemotherapeutic agents weigh between 200 and 1200 D. 45 Furthermore, the intact BBB is even less permeable to antibodies than to drugs. In a study in which the CSF penetration of the monoclonal antibody trastuzumab was investigated in six patients with breast cancer and brain metastases, the serum/CSF ratio of trastuzumab was 420:1, indicating poor penetration of the agent.…”

Section: Neurosurg Focus / Volume 21 / November 2006mentioning

confidence: 99%

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

Jahnke

Doolittle²,

Muldoon³

et al. 2006

FOC

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✓ 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 90Y 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.

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Section: Neurosurg Focus / Volume 21 / November 2006mentioning

confidence: 99%

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

Jahnke

Doolittle²,

Muldoon³

et al. 2006

FOC

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Developments in the diagnosis and treatment of primary CNS lymphoma: A prospective series

Neuwelt

Frenkel

Gumerlock

et al. 1986

Cancer

116

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Current experience with 12 patients studied prospectively suggests a new approach in the diagnosis and treatment of primary central nervous system (CNS) lymphoma, integrating the techniques of needle brain biopsy, immunohistochemical staining for monoclonal antibody and chemotherapeutic drug delivery in association with blood-brain barrier modification. Computed tomography (CT)-guided needle biopsy of deep parenchymal lesions contributed to the diagnosis in six patients. Immunohistochemical staining methods detected monoclonal immunoglobulins in those patients so tested. Following diagnosis, the patients have been treated with multi-agent chemotherapy in conjunction with osmotic blood-brain barrier modification (five without antecedent cranial irradiation) with an initial complete response rate by CT scan in nine patients, a median follow-up of 19 months from diagnosis, and a 1-year survival of 75%. This experience emphasizes the value of CT-guided stereotaxic or CT-guided needle biopsy, which limits the need for therapy without a diagnosis or the need for a major craniotomy in what are commonly deep, paraventricular lesions. Immunoperoxidase cytochemical stains can detect monoclonal immunoglobulin characteristic of CNS B-cell malignant lymphomas and provide an important diagnostic aid when only modest quantities of tissue or cells are obtained. Finally, chemotherapy administered in conjunction with osmotic blood-brain barrier modification results in a clinical response rate and survival that are at least as effective as radiotherapy as a primary therapeutic modality.

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Blood-Brain Barrier Disruption in the Treatment of Brain Tumors

Neuwelt¹,

Dahlborg²

1989

Implications of the Blood-Brain Barrier and Its Manipulation

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The need for prophylactic treatment to the central nervous system in patients with aggressive non-Hodgkin’s lymphoma

Cited by 6 publications

References 19 publications

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

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

Developments in the diagnosis and treatment of primary CNS lymphoma: A prospective series

Blood-Brain Barrier Disruption in the Treatment of Brain Tumors

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