title: 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.
abstract: 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 polymerase chain reaction (PCR) for NPM-ALK. Numbers of NPM-ALK transcripts were normalized to 10(4) copies ABL (NCNs). 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 histologic subtype. Qualitative and quantitative PCR results in BM and PB strongly correlated. BM PCR was associated with the cumulative incidence of relapses (CI-Rs): CI-R was 50% +/- 10% for 38 PCR-positive and 15% +/- 7% for 42 PCR-negative patients (P < .001). Sixteen patients with more than 10 NCNs NPM-ALK in BM had a CI-R of 71% +/- 14% compared with a CI-R of 18% +/- 6% for 59 patients with 10 or fewer NCNs (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%.
authors: Justus-Liebig-University, Department of Pediatric Hematology and Oncology, Giessen, Germany.
authors: Christine
authors: C
authors: Damm-Welk
authors: Kerstin
authors: K
authors: Busch
authors: Birgit
authors: B
authors: Burkhardt
authors: Jutta
authors: J
authors: Schieferstein
authors: Susanne
authors: S
authors: Viehmann
authors: Ilske
authors: I
authors: Oschlies
authors: Wolfram
authors: W
authors: Klapper
authors: Martin
authors: M
authors: Zimmermann
authors: Jochen
authors: J
authors: Harbott
authors: Alfred
authors: A
authors: Reiter
authors: Willi
authors: W
authors: Woessmann
mesh_terms: D001773:Blood Cells / Q000473:pathology / Q000502:physiology; D001854:Bone Marrow Cells / Q000473:pathology / Q000502:physiology*; D002648:Child; D017931:DNA Primers; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
chemical_list: D017931:DNA Primers; C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases