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-Munster Group Report.
OBJECTIVE
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.


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.


CONCLUSIONS
Six percent of childhood/adolescent NHL patients were CNS positive. However, the prevalence, pattern, and prognostic impact of CNS involvement differed among NHL subtypes.
Salzburg
Janina
J
Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany.
Burkhardt
Birgit
B
Zimmermann
Martin
M
Wachowski
Olga
O
Woessmann
Wilhelm
W
Oschlies
Ilske
I
Klapper
Wolfram
W
Wacker
Hans-Heinrich
HH
Ludwig
Wolf-Dieter
WD
Niggli
Felix
F
Mann
Georg
G
Gadner
Helmut
H
Riehm
Hansjoerg
H
Schrappe
Martin
M
Reiter
Alfred
A
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D015174:Epidural Neoplasms / Q000453:epidemiology / Q000628:therapy; D005260:Female; D005858:Germany / Q000453:epidemiology; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008228:Lymphoma, Non-Hodgkin / Q000145:classification* / Q000453:epidemiology* / Q000628:therapy; D008297:Male; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D015995:Prevalence; D011379:Prognosis; D017211:Treatment Failure; D016896:Treatment Outcome