3.5 g/m2 X 5 Responders No Multi 53 28 (14 5.6 (all) not reached one acute minimal 58

+ completed toxic death


CR = complete response; OS = overall survival; IT = intrathecal; PD = progressive disease; PFS = progression-free survival; MTX = methotrexate; BEAM + ASCT = carmustine, etoposide, cytarabine, melphalan + autologous stem cell transplant.

center treated 74 patients this way over 15 years and reported a median OS of 40 months and a 5-year OS of 42%. Ten patients experienced significant acute morbidity and mortality, but no cases of neurocognitive impairment were seen in surviving patients. There have been no randomized trials comparing conventionally administered chemotherapy to that delivered with BBB disruption. In view of this as well as the procedural complexities and acute toxicity associated with this approach, this technique has not been widely adopted.

Ongoing clinical trials are focused on adding additional agents to MTX such as thiotepa, ifosfamide, or rituximab.576061 Rituximab is a chimeric anti CD20 monoclonal antibody that improves the survival of patients with systemic diffuse large B cell lymphoma when administered with CHOP.62 Because of its physicochemical characteristics, it does not penetrate an intact BBB. Despite this, several studies are currently exploring it's use in the treatment of PCNSL.61 In addition to trying to enhance efficacy, current trials are also attempting to reduce the toxic-ity of combined modality treatment by either reducing the dose of WBXRT or deferring it entirely for patients who achieve a complete response to systemic therapy.63'64

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