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Blood, 1 December 2007, Vol. 110, No. 12, pp. 4022-4029. Prepublished online as a Blood First Edition Paper on August 24, 2007; DOI 10.1182/blood-2007-04-082040. This Article Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-04-082040v1 110/12/4022    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hagedorn, N. Articles by Eckert, C. Search for Related Content PubMed PubMed Citation Articles by Hagedorn, N. Articles by Eckert, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 20, 2007 Accepted August 10, 2007 Sub-microscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of 'isolated' and its possible clinical implications Nikola Hagedorn, Cecile Acquaviva, Eva Fronkova, Arend von Stackelberg, Andrea Barth, Udo zur Stadt, Andre Schrauder, Jan Trka, Nathalie Gaspar, Karl Seeger, Gunter Henze, Helene Cave, and Cornelia Eckert* Department of Pediatric Oncology/Hematology, Charite Medical University Berlin, Berlin, Germany Laboratoire de Biochimie Genetique -Departement de Genetique, Hopital Robert Debre (APHP), Paris, France Department of Pediatric Hematology/Oncology, 2nd Medical School, Charles University Prague, Prague, Czech Republic Department of Pediatric Hematology/Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany Service d'Hematol-immunologie pediatrique, Hopital Robert Debre, Paris, France * Corresponding author; email: cornelia.eckert{at}charite.de. 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 sub-microscopic BM involvement, which was detectable at a level of 10-4 in 46, <10-4 in 11, and non-detectable (sensitivity:10-4) in 7 patients. In the total cohort, the probability of event-free survival (pEFS) for children with BM involvement 10-4 was 0.30 (standard error [SE] ±0.09) versus 0.60 (SE±0.12) for those with <10-4 (p=0.13). The cumulative incidence of subsequent relapse was 0.24 (SE±0.01) for patients with BM involvement <10-4 and 0.65 (SE±0.01) for those with 10-4 (p=0.012). Restricted to central nervous system (CNS) relapses, pEFS was 0.11 (SE±0.09) for patients with BM involvement 10-4 and 0.63 (SE±0.17) for those with <10-4 (p=0.053). CNS relapses were associated with a higher (10-4: 80%) sub-microscopic BM involvement than testicular relapses (10-4:57%, p=0.08). In summary, we show marked heterogeneity of sub-microscopic BM involvement at first AIEM relapse diagnosis in children with ALL, and demonstrate its possible prognostic relevance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C.-H. Pui, D. Campana, D. Pei, W. P. Bowman, J. T. Sandlund, S. C. Kaste, R. C. Ribeiro, J. E. Rubnitz, S. C. Raimondi, M. Onciu, et al. Treating Childhood Acute Lymphoblastic Leukemia without Cranial Irradiation N. Engl. J. Med., June 25, 2009; 360(26): 2730 - 2741. [Abstract] [Full Text] [PDF]

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