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Relapse of TEL-AML1–Positive Acute Lymphoblastic Leukemia in Childhood: A Matched-Pair Analysis

From the Department of Pediatric Oncology/Hematology, Charité Medical Center, Humboldt-University, Berlin; Department of Pediatrics, Christian-Albrechts-Universität, Kiel; Department of Pediatric Oncology, Klinikum Buch, Berlin-Buch; and Department of Pediatric Oncology, Olgahospital, Stuttgart, Germany.

Address reprint requests to Karlheinz Seeger, MD, Department of Pediatric Oncology/Hematology, Otto-Heubner-Centrum, Charité Medical Center, Campus Virchow, Humboldt-University at Berlin, Augustenburger Platz 1, Berlin, Germany, 13353; email: karl.seeger{at}charite.de

PURPOSE: The aim of this study was to investigate whether, in relapsed childhood acute lymphoblastic leukemia (ALL), the frequent genetic feature of TEL-AML1 fusion resulting from the cryptic chromosomal translocation t(12;21)(p13;q22) is an independent risk factor.

PATIENTS AND METHODS: A matched-pair analysis was performed within a homogeneous group of children with first relapse of BCR-ABL–negative B-cell precursor (BPC) ALL treated according to relapse trials ALL-Rezidiv (REZ) of the Berlin-Frankfurt-Münster Study Group. A total of 249 patients were eligible for this study: 53 (21%) were positive for TEL-AML1, and 196 (79%) were negative. Positive patients were matched for established most-significant prognostic determinants at relapse, time point, and site of relapse, as well as age and peripheral blast cell count at relapse.

RESULTS: Fifty pairs matching the aforementioned criteria could be determined. The probabilities with SE of event-free survival and survival at 5 years for matched TEL-AML1 positives and negatives are 0.63 ± 0.10 versus 0.38 ± 0.10 (P = .09) and 0.82 ± 0.09 versus 0.42 ± 0.19 (P = .10), respectively. These results were confirmed by multivariate analysis, revealing an independent prognostic significance of time point and site of relapse (both P < .001) but not of TEL-AML1 expression (P = .09).

CONCLUSION: TEL-AML1 expression does not constitute an independent risk factor in relapsed childhood BCP-ALL after matching for relevant prognostic parameters. It undoubtedly characterizes genetically an ALL entity associated with established favorable prognostic parameters. High-risk therapeutic procedures such as allogeneic SCT should be considered restrictively.

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