Treatment For Relapsed Or Refractory Disease

The majority of patients with PCNSL relapse following primary treatment, and a significant minority have progressive disease during primary treatment. One retrospective study of 173 patients concluded that patients whose overall condition is suitable to receive salvage therapy have significantly prolonged survival compared to those who are given no further treatment (14 vs 2 months).69 Although this improved survival may be largely due to patient, rather than treatment-related factors, fit patients should be offered salvage treatment. However, there are no standard recommendations for second-line therapy as most studies are small case series of heterogeneously treated patients. The choice of treatment depends on the patient's prior treatment, the site of relapse (brain, ocular, lep-tomeningeal, spinal, systemic, or a combination), and the disease-free interval.

Patients who relapse in the brain following WBXRT (either alone or as part of combined modality treatment) should be offered chemotherapy. MTX can be administered to those who did not receive it during first line therapy, although neurotoxicity remains a concern with this sequence of therapy. Several chemotherapy options have been reported to be useful for those who progress or relapse soon after MTX-based combined modality treatment. These include high-dose cytarabine (3g/m2),70 PCV (procarbazine, lomustine, and vincristine),71 thiotepa, temozo-lamide,72 and topotecan.73,74 High-dose chemotherapy with thiotepa, busulfan, and cyclophosphamide followed by autologous peripheral blood stem cell (PBSC) infusion can result in 64% survival at 3 years, but was too toxic for patients over 60 years of age. Of the 22 patients who were treated with this approach, 14 had received CYVE (cytarabine and etoposide) to ascertain chemosensitivity prior to high-dose treatment.75 There are ongoing studies using rituximab intravenously for relapsed disease.76'77

WBXRT can be used at progression or relapse if it was not part of the initial therapy. One study reported an overall response of 76 % and a median survival of 6.8 months with this strategy while another reported a

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