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CNS Involvement in Children With Newly Diagnosed Non-Hodgkin’s Lymphoma

From the Departments of Hematology/Oncology, Radiation Therapy, Pathology and Laboratory Medicine, and Biostatistics, St Jude Children’s Research Hospital, and University of Tennessee at Memphis, College of Medicine, Memphis, TN; and Department of Pediatrics, Northwestern University School of Medicine, and Children’s Memorial Hospital, Chicago, IL.

Address reprint requests to John T. Sandlund, MD, Department of Hematology-Oncology, St Jude Children’s Research Hospital, 332 N Lauderdale, Memphis, TN 38101; email john.sandlund{at}stjude.org

PURPOSE: To determine the frequency of CNS involvement at diagnosis of non-Hodgkin’s lymphoma (NHL), to characterize its pattern of presentation, and to determine its prognostic significance.

PATIENTS AND METHODS: We reviewed the records of 445 children (1975 through 1995) diagnosed with NHL (small noncleaved cell NHL/B-cell acute lymphoblastic leukemia [SNCC NHL/B-ALL], 201 patients; lymphoblastic, 113; large cell, 119; other, 12). Tumor burden was estimated by serum lactate dehydrogenase (LDH) measurement and reclassification of disease stage irrespective of CNS involvement (modified stage).

RESULTS: Thirty-six of 445 children with newly diagnosed NHL had CNS involvement (lymphoma cells in the CSF [n = 23], cranial nerve palsy [n = 9], both features [n = 4]), representing 13%, 7%, and 1% of small noncleaved cell lymphoma, lymphoblastic lymphoma, and large-cell cases, respectively. By univariate analysis, CNS disease at diagnosis did not significantly impact event-free survival (P = .095), whereas stage and LDH did; however, children with CNS disease at diagnosis were at 2.0 times greater risk of death than those without CNS disease at diagnosis. In a multivariate analysis, CNS disease was not significantly associated with either overall or event-free survival, whereas both serum LDH and stage influenced both overall and event-free survival. Among cases of SNCC NHL/B-ALL, CNS disease was significantly associated with event-free and overall survival (univariate analysis); however, in multivariate analysis, only LDH had independent prognostic significance. Elevated serum LDH or higher modified stage were associated with a trend toward poorer overall survival among children with CNS disease.

CONCLUSION: A greater tumor burden at diagnosis adversely influences the treatment outcome of children with NHL and CNS disease at diagnosis, suggesting a need for ongoing improvement in both systemic and CNS-directed therapy.

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