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Prevalence, Clinical Pattern, and Outcome of CNS Involvement in Childhood and Adolescent Non-Hodgkin's Lymphoma Differ by Non-Hodgkin's Lymphoma Subtype: A Berlin-Frankfurt-Münster Group Report

Janina Salzburg, Birgit Burkhardt, Martin Zimmermann, Olga Wachowski, Wilhelm Woessmann, Ilske Oschlies, Wolfram Klapper, Hans-Heinrich Wacker, Wolf-Dieter Ludwig, Felix Niggli, Georg Mann, Helmut Gadner, Hansjoerg Riehm, Martin Schrappe, Alfred Reiter

From the Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen; Department of Hematopathology and Lymph Node Registry, and Children's University Hospital, University Hospital Schleswig-Holstein, Campus Kiel, Kiel; Department of Hematology, Oncology, and Tumor Immunology, Robert-Rössle-Clinic at the HELIOS Klinikum Berlin-Buch, Charité Medical School, Berlin; Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany; Department of Pediatric Hematology and Oncology, Children's University Hospital Zurich, Zurich, Switzerland; and Department of Pediatric Hematology and Oncology, St Anna Children's Hospital, Vienna, Austria

Address reprint requests to Alfred Reiter, MD, NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, Justus-Liebig-University, D-35385 Giessen, Germany; e-mail: alfred.reiter{at}paediat.med.uni-giessen.de

Purpose: We analyzed the prevalence, clinical pattern, and prognostic impact of CNS involvement in a large cohort of children and adolescents diagnosed with non-Hodgkin's lymphoma (NHL), with special attention to differences according to NHL subtype.

Patients and Methods: From October 1986 to December 2002, 2,381 patients (median age, 9.37 years; range, 0.2 to 23.8 years; female-to-male ratio, 1:2.7) from Germany, Austria, and Switzerland were registered. A total of 2,086 patients were eligible for the consecutive multicenter protocols NHL–Berlin-Frankfurt-Münster [BFM] -86, NHL-BFM-90, and NHL-BFM-95, and could be evaluated for outcome.

Results: CNS involvement was diagnosed in 141 (5.9%) of 2,381 patients and was associated with an advanced stage of NHL. The percentage of CNS-positive patients was 8.8% for Burkitt's lymphoma/Burkitt's leukemia (BL/B-ALL), 5.4% for precursor B–lymphoblastic lymphoma (pB-LBL), 3.3% for anaplastic large-cell lymphoma, 3.2% for T-cell–LBL, 2.6% for diffuse large B-cell lymphoma, and 0% for primary mediastinal large B-cell NHL (P < .001). Most CNS-positive patients with pB-LBL, T-LBL, or BL/B-ALL had meningeal disease. The probability of event-free survival (pEFS; ± SE) at 5 years was 85% ± 1% for the 2,086 protocol patients (median follow-up, 6.5 years; range, 0.3 to 17.7 years). For the 112 CNS-positive patients, pEFS was 64% ± 5%, compared with 86% ± 1% for the 1,927 CNS-negative patients (P < .001). Although CNS disease had no impact on pEFS for advanced-stage T-LBL patients, CNS-positive patients with BL/B-ALL had a worse average outcome than CNS-negative patients with stage IV BL/B-ALL (60% ± 5% v 81% ± 3%; P < .001). In multivariate analysis, CNS disease was the strongest predictor for relapse in BL/B-ALL patients with advanced-stage disease.

Conclusion: Six percent of childhood/adolescent NHL patients were CNS positive. However, the prevalence, pattern, and prognostic impact of CNS involvement differed among NHL subtypes.

Supported by the Deutsche Krebshilfe, Bonn, Germany.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.