Impaired CD163-mediated hemoglobin-scavenging and severe toxic symptoms in patients treated with gemtuzumab ozogamicin.
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.
Department of Clinical Biochemistry, Arhus Sygehus, Aarhus University Hospital, Aarhus, Denmark.
Maciej Bogdan
MB
Maniecki
Henrik
H
Hasle
Lennart
L
Friis-Hansen
Birgitte
B
Lausen
Ove Juul
OJ
Nielsen
Knud
K
Bendix
Søren Kragh
SK
Moestrup
Holger Jon
HJ
Møller
D000617:Aminoglycosides / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D000079982:Gemtuzumab; D006242:Haptoglobins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006461:Hemolysis; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000188:drug therapy; D008297:Male; D011956:Receptors, Cell Surface / Q000097:blood*; D051116:Receptors, Scavenger; D013577:Syndrome; D000098902:CD163 Antigen
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006242:Haptoglobins; D006454:Hemoglobins; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; C035492:haptoglobin-hemoglobin complex; D000079982:Gemtuzumab