A substantial proportion of patients in our series received palliative treatment or no treatment at all. Given that elevated lactate dehydrogenase was a common feature in our cohort (58% of patients) and in other large series of PTCL,23,24  we believe this factor might be of limited importance as a predictor for CNS relapse in PTCL. No CNS events occurred in patients with angioimmunoblastic T-cell lymphoma (n = 40), hepatosplenic T-cell lymphoma (n = 10), or enteropathy-associated T-cell lymphoma (n = 4). All cases were reviewed at our institution for confirmation of diagnosis. Twenty-eight (4.5%) of 625 patients experienced a progression or relapse that involved the CNS, with a median time to CNS event of 4.3 months (range, 1.1-30 months). Each pathology report was retrospectively reviewed to avoid incorrect registry entries and for classification according to the 2008 edition of the World Health Organization classification of lymphoid neoplasms.21  Cases not fulfilling criteria for T-cell lymphoma or fulfilling criteria for precursor T-cell malignancies, primary cutaneous lymphomas, and leukemic forms were excluded from the study. Study of radiolabeled indium-111 and yttrium-90 ibritumomab tiuxetan in primary central nervous system lymphoma, High-dose methotrexate with or without rituximab in newly diagnosed primary CNS lymphoma, Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: Results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study, Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in an elderly population: An intergroup ANOCEF-GOELAMS randomised phase 2 trial, Recurrent intrathecal methotrexate induced neurotoxicity in an adolescent with acute lymphoblastic leukemia: Serial clinical and radiologic findings, Prophylactic intrathecal chemotherapy in primary CNS lymphoma. Ongoing trials that randomly assign patients to different consolidation treatments will hopefully shed more light on the optimal consolidation regimen. CNS relapse was defined as CNS involvement at any time after initial diagnosis and classified as isolated if no evidence of lymphoma relapse or progression outside the CNS was present. The multicenter Cancer and Leukemia Group B (CALGB) study 50202 used rituximab, HD-MTX, and temozolomide (R-MT), followed by consolidation with high-dose etoposide and cytarabine. Treatment of PCNSL has evolved over the last decades, but no uniform consensus on the optimal treatment regimen exists currently. Taking into account the rarity of CNS spread, the poor outcomes in relapsed patients with PTCL is largely driven by the lack of effective salvage treatment of systemic disease. Contribution: F.E., M.J., and T.R. In our series, all cases with radiological findings in the leptomeninges also had cytological findings consistent with lymphoma involvement in the cerebrospinal fluid. The prognosis of patients with PCNSL has improved during the last decades with the introduction of high-dose methotrexate. The publication costs of this article were defrayed in part by page charge payment. Very few patients had involvement of some particular organs, such as testicles or kidneys, which has been associated with a high incidence of CNS relapse in aggressive NHL,8,25  and the low number of patients in combination with the rarity of CNS involvement becomes a major limitation of our study in this aspect.

Focal radiation resulted in increased relapses in regions excluded from the radiation port, confirming the need for WBRT in PCNSL47 when radiotherapy is used. Permissions, Authors Factors with P ≤ .1 for CNS relapse in univariable Cox proportional hazards regression and tested in the multivariable model are listed in Table 3.

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