SEARCH:   Advanced

Blood, 15 November 2008, Vol. 112, No. 10, pp. 3982-3988. Prepublished online as a Blood First Edition Paper on September 9, 2008; DOI 10.1182/blood-2008-06-164129. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2008-06-164129v1 112/10/3982    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Dworzak, M. N. Articles by Gadner, H. Search for Related Content PubMed PubMed Citation Articles by Dworzak, M. N. Articles by Gadner, H. Related Collections Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy Michael N. Dworzak1, Angela Schumich1, Dieter Printz1, Ulrike Pötschger1, Zvenyslava Husak1, Andishe Attarbaschi2, Giuseppe Basso3, Giuseppe Gaipa4, Richard Ratei5, Georg Mann2, and Helmut Gadner1,2 1 Children's Cancer Research Institute, Vienna, Austria; 2 St Anna Children's Hospital, Vienna, Austria; 3 Laboratory of Pediatric Onco-Hematology, Department of Pediatrics, University Hospital of Padova, Padova, Italy; 4 Tettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, Ospedale San Gerardo, Monza, Italy; and 5 Department of Hematology, Oncology and Tumor Immunology, Robert-Roessle-Clinic at the HELIOS Klinikum Berlin, Charité Medical School, Berlin, Germany CD20 is expressed in approximately one- half of pediatric acute lymphoblastic leukemia (ALL) cases with B-cell precursor (BCP) origin. We observed that it is occasionally up-regulated during treatment. To understand the impact of this on the potential effectiveness of anti-CD20 immunotherapy, we studied 237 CD10+ pediatric BCP-ALL patients with Berlin-Frankfurt-Munster (BFM)–type therapy. We analyzed CD20 expression changes from diagnosis to end-induction, focusing on sample pairs with more than or equal to 0.1% residual leukemic blasts, and assessed complement-induced cytotoxicity by CD20-targeting with rituximab in vitro. CD20-positivity significantly increased from 45% in initial samples to 81% at end-induction (day 15, 71%). The levels of expression also increased; 52% of cases at end-induction had at least 90% CD20pos leukemic cells, as opposed to 5% at diagnosis (day 15, 20%). CD20 up-regulation was frequent in high-risk patients, patients with high minimal residual disease at end-induction, and patients who suffered later from relapse, but not in TEL/AML1 cases. Notably, up-regulation occurred in viable cells sustaining chemotherapy. In vitro, CD20 up-regulation significantly enhanced rituximab cytotoxicity and could be elicited on prednisolone incubation. In conclusion, CD20 up-regulation is frequently induced in BCP-ALL during induction, and this translates into an acquired state of higher sensitivity to rituximab. This study was registered at http://www.clinicaltrials.gov as #NCT00430118 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Irving, J. Jesson, P. Virgo, M. Case, L. Minto, L. Eyre, N. Noel, U. Johansson, M. Macey, L. Knotts, et al. Establishment and validation of a standard protocol for the detection of minimal residual disease in B lineage childhood acute lymphoblastic leukemia by flow cytometry in a multi-center setting; Haematologica, June 1, 2009; 94(6): 870 - 874. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020