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Blood, 15 July 2007, Vol. 110, No. 2, pp. 670-677.
Prepublished online as a Blood First Edition Paper on March 28, 2007; DOI 10.1182/blood-2007-02-066852.
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Submitted February 2, 2007
Accepted March 24, 2007
Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK positive anaplastic large cell lymphoma
Christine Damm-Welk, Kerstin Busch, Birgit Burkhardt, Jutta Schieferstein, Susanne Viehmann, Ilske Oschlies, Wolfram Klapper, Martin Zimmermann, Jochen Harbott, Alfred Reiter*, and Willi Woessmann
Department of Pediatric Hematology & Oncology, Justus-Liebig-University, Giessen, Germany
Department of Pathology, Hematopathology Section, and Lymph Node Registry, University Hospital Schleswig-Holstein, Kiel, Germany
* Corresponding author; email: alfred.reiter{at}paediat.med.uni-giessen.de.
Clinical and histopathological characteristics have limited prognostic value for children with anaplastic large cell lymphoma (ALCL). We evaluated the presence, extent, and prognostic impact of circulating tumor cells in bone marrow (BM) and peripheral blood (PB) of children and adolescents with NPM-ALK--positive ALCL at diagnosis using qualitative and quantitative PCR for NPM-ALK. Numbers of NPM-ALK transcripts were normalized to 104 copies ABL (NCN). BM was analyzed from 80 patients and PB from 52. BM was positive for NPM-ALK in 47.5% of patients, and positivity was significantly correlated with clinical stage, mediastinal or visceral involvement, microscopic BM involvement, and histological subtype. Qualitative and quantitative PCR results in BM and PB strongly correlated. BM PCR was associated with the cumulative incidence of relapses (CI-R): CI-R was 50±10% for 38 PCR-positive and 15±7% for 42 PCR-negative patients (P < .001). Sixteen patients with >10 NCN NPM-ALK in BM had a CI-R of 71±14% compared to a CI-R of 18±6% for 59 patients with 10 NCN (P <.001). PB PCR results led to a similar grouping. Thus, quantitative PCR in BM or PB allows identification of 20% of patients experiencing 60% of all relapses with an event-free survival of 20%.

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