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Søren Kragh Moestrup

Impaired CD163 Mediated Hemoglobin-Scavenging and Hemolytic Crisis in Patients Treated with CD33 Targeted Chemotherapy (Gemtuzumab Ozogamicin, MylotargTM)

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  • Maciej Bogdan Maniecki, Denmark
  • Henrik Hasle
  • Lennart Friis-Hansen, University of Copenhagen, Denmark
  • Birgitte Lausen, University of Copenhagen, Denmark
  • Ove Juul Nielsen, University of Copenhagen, Denmark
  • Knud Bendix, Denmark
  • Søren Kragh Moestrup
  • Holger Jon Møller
  • The Department of Paediatrics
  • Department of Medical Biochemistry
  • Clinical Biochemistry
  • The Department of Pathology
Hemoglobin liberated to plasma during intravascular hemolyses is rapidly bound to haptoglobin. The hemoglobin-haptoglobin complexes undergo endocytosis through the monocyte/macrophage specific scavenger receptor for hemoglobin (CD163). This mechanism protects against oxidative and NO-scavenging adverse effects of free hemoglobin. In this study, we describe a novel syndrome of severe intravascular hemolysis and serious hemolytic crisis due to impaired hemoglobin scavenging in three acute myeloid leukemia patients following CD33-directed therapy with the immunotoxin gemtuzumab ozogamicin (GO, MylotargTM). A synchronous high free 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 bone marrow macrophages 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 patients had severe inflammation and serious organ failure symptoms that may be a direct effect of the persistent high level of free hemoglobin. One of the patients had a fatal outcome whereas, the other two recovered from the hemolytic episode, and the peripheral blood CD163 expression returned to normal. The risk of a serious hemolytic crisis should be considered following CD33-targeted chemotherapy. Furthermore, the cases provide circumstantial evidence of a key role of CD163 plasma hemoglobin clearance in vivo.
Original languageEnglish
JournalBlood
Issue3684
ISSN0006-4971
Publication statusPublished - 2007
EventAnnual Meeting of the American Society of Hematology - Atlanta, United States
Duration: 6 Dec 200711 Dec 2007
Conference number: 49

Conference

ConferenceAnnual Meeting of the American Society of Hematology
Number49
CountryUnited States
CityAtlanta
Period06/12/200711/12/2007

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