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Purpose of Review: 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 Findings: 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., Summary: 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.

Background: The use of antilymphocyte antibodies for induction therapy or for treatment for rejection has been associated with an increased risk of posttransplant lymphoproliferative disorder (PTLD). The authors investigated the incidence of PTLD after monoclonal antilymphocyte, polyclonal antilymphocyte, interleukin (IL)-2 receptor antibody, or no induction therapy in primary kidney transplant recipients., Methods: A multivariate Cox analysis of 38,519 primary kidney transplants from January 1, 1997, to December 31, 2000, was performed to compare the incidence of PTLD, graft survival, and patient survival among the induction groups., Results: The actual incidence of PTLD was 0.85% in 2,713 recipients with monoclonal, 0.81% in 4,343 with polyclonal, 0.50% in 7,800 with IL-2, and 0.51% in 23,663 recipients with no induction therapy (P=0.02). The Cox model indicated that as compared with no induction, the increased risk of PTLD was 72% with monoclonal (P=0.03), 29% with polyclonal (P=0.27), and 14% with IL-2 induction (P=0.52). IL-2 receptor antibody was associated with a 17% reduced risk of graft loss (P=0.002) and a 21% reduced risk of mortality (P=0.005) compared with no induction. Monoclonal and polyclonal induction therapies were not associated with a reduced risk of graft loss or mortality. Mycophenolate mofetil discharge maintenance immunosuppression was associated with a significantly reduced risk of PTLD and graft loss compared with azathioprine., Conclusions: Among induction therapies, IL-2 receptor antibody induction was associated with the smallest risk of PTLD and improved graft and patient survival. Monoclonal or polyclonal induction was not associated with improved graft or patient survival, and monoclonal induction was associated with an increased risk of PTLD.

Background: Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of transplantation for which new therapies are being explored, including cytotoxic T-cell infusion and anti-CD20 antibody. Whether the PTLD is of donor cell or recipient cell origin influences the type of cytotoxic T-cell therapy, in view of the MHC-restricted nature of the immune response. The efficacy of anti-CD20 therapy, on the other hand, depends on CD20 expression by neoplastic cells. Only limited prior data exist regarding either of these parameters., Methods: Materials for this study were obtained in part from a Southwest Oncology Group clinical trial of solid organ transplant patients with PTLD. Tumor tissue from 21 patients (15 heart, 4 lung, and 2 kidney recipients) was evaluated for donor versus recipient origin by analyzing DNA at multiple polymorphic microsatellites., Results: Twenty tumors (95%) were of recipient origin. Anatomically separate tumors from a given patient had the same origin. A single PTLD of donor origin arose in donor lung. Epstein-Barr virus (EBV), as assessed by EBER and LMP1 histochemical stains, was present in 16 of 17 tumors. CD20, evaluated immunohistochemically, was expressed diffusely in 12 of 17 tumors and focally in 3 and was undetectable in 2 tumors., Conclusions: PTLD after solid organ transplantation is frequently EBV-related and of recipient origin, implying that therapeutic EBV-specific T cells must be matched to the HLA type of the recipient, not that of the donor, in most cases of PTLD. Variable CD20 expression among tumors suggests that in some patients anti-CD20 therapy might be more effective in combination with other therapies.