Primary central nervous system lymphoma in children and adolescents: low relapse rate after treatment according to Non-Hodgkin-Lymphoma Berlin-Frankfurt-Münster protocols for systemic lymphoma | Haematologica

摘要

Primary central nervous system lymphoma (PCNSL) represents a rare subtype of non-Hodgkin lymphoma (NHL) restricted to the CNS. In adults, PCNSL is associated with a poor prognosis.1 Patients with predisposing conditions such as immunodeficiency have an increased risk of PCNSL.2 In children, very little is known about PCNSL. The International Primary CNS Lymphoma Collaborative Group (IPCG) reported a retrospective collection of 29 PCNSL patients who had been treated with various treatment strategies.3 Another retrospective review from North America identified 12 PCNSL patients,4 and the recent retrospective mono-center experience of the Seoul Children Hospital reported 6 patients treated with relapse-free survival achieved in 5.5 Taking these cases together with earlier case reports,2,4,6–10 far less than 100 cases of PCNSL in children and adolescents have been published so far.In the current study of the population-based NHL-BFM data (Berlin-Frankfurt-Muenster), the frequency, clinical characteristics, diagnostic difficulties, treatment and outcome of 17 pediatric PCNSL patients are discussed. All patients were uniformly diagnosed and treated according to NHL-BFM protocols. The study aims to add relevant information to the ongoing discussion concerning optimal treatment. Also, the description of the prolonged and difficult diagnosis and differential diagnosis procedures in the current report might raise awareness of pediatric patients with PCNSL.Children and adolescents diagnosed with any subtype of NHL were registered with the NHL-BFM-center after patients and/or guardians gave informed consent. Standard staging investigations included examination of cerebrospinal fluid (CSF), cranial computed tomography (CT) and/or cranial magnetic resonance imaging (MRI). CNS disease was diagnosed in patients with intracerebral/intraspinal mass(es) (ICM) and/or cranial nerve palsy (CNP) not caused by an extradural mass and/or blasts in the CSF. Epidural NHL was not considered as CNS disease. NHL was classified according to WHO classification and centrally reviewed by NHL-BFM reference pathologists, except for Patients 4 and 12. CSF slides were centrally reviewed by 3 of the authors (WW, AR, BB). Patients were treated according to the NHL-BFM90,11 NHL-BFM9512 or B-NHL BFM0413 protocols. Institutional review board approvals were obtained before patients were included in the study.For statistical analyses, differences between subgroups were examined by χ2 test or Fisher’s exact test. Probability of survival (pOS) was calculated from diagnosis to first event (death, progression/relapseon-response, second malignancy) or to last follow up using the Kaplan-Meier method. Differences were compared using the log rank test, and the standard error (SE) was calculated according to Greenwood. Statistical analysis was performed using the SAS program v.9.13 (SAS Institute Inc., Cary, NC, USA).Among 3740 pediatric or adolescent NHL patients registered between 1990 and 2011, 17 patients with PCNSL were identified: 12 immunocompetent and 5 immunocompromised. Median age was 13.3 years (range 1.3–17.9 years). The histological diagnosis was peripheral T-cell lymphoma (PTCL) in one patient, anaplastic large cell lymphoma (ALCL) in 5 patients, and mature aggressive B-cell lymphoma (B-NHL) in 11 patients (Figure 1). Epstein-Barr encoding region (EBER) in situ hybridization to identify Epstein-Barr virus (EBV) antigens in the lymphoma tissue was performed in 5 patients (Patients 1, 5, 14, 15 and 16), and was positive in one (Patient 1) and negative in 4 samples. In all but one patient (Patient 2), CT/MRI showed solid CNS lymphoma manifestation(s) including one patient (Patient 13) with one large intraspinal manifestation. Six patients (38%) had multiple intracerebral lesions. One patient was diagnosed with primary leptomeningeal disease with 1000 lymphoma cells/μL CSF and cranial nerve palsy (Patient 2).Download figureOpen in new tabDownload powerpointFigure 1. P