Primary central nervous system lymphoma: recent progress, many remaining questions

To review what progress has been made in the treatment of primary central nervous system lymphoma since the time when it was first recognized that high-dose methotrexate based chemotherapy improved outcome over radiation therapy alone.

Recent work has explored the use of high-dose methotrexate alone; the optimum dose of methotrexate; the need for intrathecal therapy; combinations of other drugs with high-dose methotrexate, most notably alkylators, high-dose cytarabine, and rituximab; and the use of myeloablative chemotherapy and autologous stem-cell rescue. Recent progress has also been made in the identification of clinical prognostic factors, and in identifying underlying biologic properties that may account for this tumor's distinctive clinical behavior.

Further improvement in progression-free survival and in the proportion of patients achieving long-term disease-free survival does seem to be achievable, based on the results of nonrandomized data. Reduction in the risk of severe neurotoxicity by withholding or deferring radiation therapy also appears feasible. Existing treatment options can be individualized to the patient's circumstances. However, the optimal management of primary central nervous system lymphoma remains to be defined, and participation in a suitable clinical trial is highly appropriate.