title: Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of "isolated" and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group.
abstract: This study investigates the extent of bone marrow (BM) involvement at diagnosis of apparent isolated extramedullary (AIEM) relapses of childhood acute lymphoblastic leukemia (ALL) and its relation to prognosis. Sixty-four children with first AIEM relapse treated in Germany, Czech Republic, or France were included. Real-time quantitative polymerase chain reaction using T-cell receptor and immunoglobulin gene rearrangements provided a sensitive measure of submicroscopic BM involvement, which was detectable at a level of 10(-4) or higher in 46 patients and less than 10(-4) in 11 patients, and was nondetectable (sensitivity: 10(-4)) in 7 patients. In the total cohort, the probability of event-free survival (pEFS) for children with BM involvement of 10(-4) or higher was 0.30 (0.09 +/- SE) versus 0.60 (+/- 0.12) for those with less than 10(-4) (P = .13). The cumulative incidence of subsequent relapse was 0.24 (+/- 0.01) for patients with BM involvement less than 10(-4) and 0.65 (+/- 0.01) for those with 10(-4) or higher (P = .012). Restricted to central nervous system (CNS) relapses, pEFS was 0.11 (+/- 0.09) for patients with BM involvement 10(-4) or higher and 0.63 (+/- 0.17) for those with less than 10(-4) (P = .053). CNS relapses were associated with a higher (> or = 10(-4): 80%) submicroscopic BM involvement than testicular relapses (> or = 10(-4): 57%, P = .08). In summary, we show marked heterogeneity of submicroscopic BM involvement at first AIEM relapse diagnosis in children with ALL, and demonstrate its possible prognostic relevance.
authors.affiliation: Department of Pediatric Oncology/Hematology, Charité Medical University Berlin, Berlin, Germany.
authors.forename: Nikola
authors.initials: N
authors.lastname: Hagedorn
authors.forename: Cécile
authors.initials: C
authors.lastname: Acquaviva
authors.forename: Eva
authors.initials: E
authors.lastname: Fronkova
authors.forename: Arend
authors.initials: A
authors.lastname: von Stackelberg
authors.forename: Andrea
authors.initials: A
authors.lastname: Barth
authors.forename: Udo
authors.initials: U
authors.lastname: zur Stadt
authors.forename: André
authors.initials: A
authors.lastname: Schrauder
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gaspar
authors.forename: Karl
authors.initials: K
authors.lastname: Seeger
authors.forename: Günter
authors.initials: G
authors.lastname: Henze
authors.forename: Hélène
authors.initials: H
authors.lastname: Cavé
authors.forename: Cornelia
authors.initials: C
authors.lastname: Eckert
mesh_terms: D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012008:Recurrence; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D015996:Survival Rate
chemical_list: D011948:Receptors, Antigen, T-Cell