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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 (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 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 Moller, H. J. Search for Related Content PubMed PubMed Citation Articles by Maniecki, M. B. Articles by Moller, H. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 24, 2007 Accepted May 17, 2008 Impaired CD163-mediated hemoglobin-scavenging and severe toxic symptoms in patients treated with gemtuzumab ozogamicin Maciej Bogdan Maniecki, Henrik Hasle, Lennart Friis-Hansen, Birgitte Lausen, Ove Juul Nielsen, Knud Bendix, Soren Kragh Moestrup, and Holger Jon Moller* Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Biochemistry, Copenhagen University Hospital, Copenhagen, Denmark Pediatric Clinic II, Juliane Marie Centre, Copenhagen University Hospital, Copenhagen, Denmark Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark Institute of Medical Biochemistry, University of Aarhus, Aarhus, Denmark * Corresponding author; email: hjmol{at}as.aaa.dk. We describe a novel syndrome of severe toxic symptoms during intravascular hemolysis due to impaired hemoglobin scavenging in two children with acute myeloid leukemia undergoing CD33-directed therapy with the immunotoxin gemtuzumab ozogamicin (GO, MylotargTM). 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 following CD33-targeted chemotherapy when the disease is complicated by a pathological 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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