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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1510-1514. Prepublished online as a Blood First Edition Paper on June 11, 2008; DOI 10.1182/blood-2007-09-114165. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-09-114165v1 112/4/1510    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 Maniecki, M. B. Articles by Møller, H. J. Search for Related Content PubMed PubMed Citation Articles by Maniecki, M. B. Articles by Møller, H. J. Related Collections Red Cells Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Brief Report Impaired CD163-mediated hemoglobin-scavenging and severe toxic symptoms in patients treated with gemtuzumab ozogamicin Maciej Bogdan Maniecki1, Henrik Hasle2, Lennart Friis-Hansen3, Birgitte Lausen4, Ove Juul Nielsen5, Knud Bendix6, Søren Kragh Moestrup1,7, and Holger Jon Møller1 1 Department of Clinical Biochemistry, Århus Sygehus, Aarhus University Hospital, Aarhus; 2 Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus; 3 Department of Clinical Biochemistry, 4 Pediatric Clinic II, Juliane Marie Centre, and 5 Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen; 6 Institute of Pathology, Århus Sygehus, Aarhus University Hospital, Aarhus; and 7 Institute of Medical Biochemistry, University of Aarhus, Aarhus, Denmark We describe a novel syndrome of severe toxic symptoms during intravascular hemolysis due to impaired hemoglobin scavenging in 2 children with acute myeloid leukemia undergoing CD33-directed therapy with the immunotoxin gemtuzumab ozogamicin (GO). A simultaneous high plasma hemoglobin, haptoglobin, and low bilirubin after septicemia-induced intravascular hemolysis indicated abrogated clearance of haptoglobin-hemoglobin complexes. This was further supported by low levels of plasma soluble CD163 and a concordant low number of CD163-expressing monocytes. We show that CD163 positive monocytes and macrophages from liver, spleen, and bone marrow coexpress CD33, thus suggesting that the GO-induced cellular cytotoxicity of CD33 positive cells eradicates a significant part of the CD163 positive monocytes and macrophages. The risk of severe toxic symptoms from plasma hemoglobin should be considered after CD33-targeted chemotherapy when the disease is complicated by a pathologic intravascular hemolysis. Furthermore, the cases provide further circumstantial evidence of a key role of (CD163-expressing) monocytes/macrophages in plasma hemoglobin clearance in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. J. Nielsen and S. K. Moestrup Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging Blood, July 23, 2009; 114(4): 764 - 771. [Abstract] [Full Text] [PDF] P. W. Buehler, B. Abraham, F. Vallelian, C. Linnemayr, C. P. Pereira, J. F. Cipollo, Y. Jia, M. Mikolajczyk, F. S. Boretti, G. Schoedon, et al. Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification Blood, March 12, 2009; 113(11): 2578 - 2586. [Abstract] [Full Text] [PDF]

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