Primary CNS Posttransplant Lymphoproliferative Disease (PTLD): An International Report of 84 Cases in the Modern Era

Abstract

We performed a multicenter, International analysis of solid organ transplant (SOT)-related primary central nervous system (PCNS) posttransplant lymphoproliferative disease (PTLD). Among 84 PCNS PTLD patients, median time of SOT-to-PTLD was 54 months, 79% had kidney SOT, histology was monomorphic in 83% and tumor was EBVþ in 94%. Further, 33% had deep brain involvement, 10% had CSF involvement, while none had ocular disease. Immunosuppression was reduced in 93%; additional first-line therapy included high-dose methotrexate (48%), high-dose cytarabine (33%), brain radiation (24%) and/or rituximab (44%). The overall response rate was 60%, while treatment-related mortality was 13%. With 42-month median follow-up, three-year progression-free survival (PFS) and overall survival (OS) were 32% and 43%, respectively. There was a trend on univariable analysis for improved PFS for patients who received rituximab and/or high-dose cytarabine. On multivariable Cox regression, poor performance status predicted inferior PFS (HR 2.61, 95% CI 1.32-5.17, p ¼ 0.006), while increased LDH portended inferior OS (HR 4.16, 95% CI 1.29-13.46, p ¼ 0.02). Moreover, lack of response to first-line therapy was the most dominant prognostic factor on multivariable analysis (HR 8.70, 95% CI 2.56-29.57, p ¼ 0.0005). Altogether, PCNS PTLD appears to represent a distinct clinicopathologic entity within the PTLD spectrum that is associated with renal SOT, occurs late, is monomorphic and retains EBV positivity.

Complete and Durable Responses in Primary Central Nervous System Posttransplant Lymphoproliferative Disorder with Zidovudine, Ganciclovir, Rituximab, and Dexamethasone

“…The most common therapeutic options after reduction in immune suppression therapy include cytotoxic chemotherapy with high dose methotrexate (HD-MTX), with or without whole brain radiotherapy (WBRT) 13 . A 2013 multicenter retrospective review by Evens et al analyzed first line treatment after reduction of immune suppression in 84 PCNS-PTLD patients over a 14 year period 12 . HD-MTX was given to 48% of the cohort alone or in combination with other agents.…”

Primary Central Nervous System Immunomodulatory Therapy-Induced Lymphoproliferative Disorder in a Patient with Ulcerative Colitis: A Case Report and Review of the Literature

“…Evens et al reported on 84 patients in which 37% of the lesions were multifocal. Deep brain involvement was seen in 33% of cases 9 . In a case series of 10 patients, the lesions were multifocal in 7 patients and solitary in 3 cases 16 .…”

“…The first report of CNS involvement was in the posttransplant setting (PTLD) 27 . Following this initial description, primary CNS PTLD became a well-documented entity 2,[4][5][6]9,14,16 The mean interval between transplantation and the onset of primary CNS PTLD is approximately 4 years, (1.8-11.4 years) 14 . The median age at the time of primary CNS PTLD diagnosis is 50 years (18-77 years).…”

“…93%) had reduction of immunosuppression as part of their first-line treatment9 . Additional firstline therapy was otherwise heterogeneous.…”

A Rare Presentation of Isolated CNS Posttransplantation Lymphoproliferative Disorder

“…CNS disease has previously been characterized by multifocal lesions, most commonly in the cerebral hemispheres involving subcortical white matter or basal ganglia. Isolated CNS PTLD is typically monomorphic and consistently more aggressive than its systemic counterpart [5]. Long-term prognosis of central nervous system PTLD is considered extremely poor [3, 4, 6, 7].…”