Impaired CD163-mediated hemoglobin-scavenging and severe toxic symptoms in patients treated with gemtuzumab ozogamicin

Blood. 2008 Aug 15;112(4):1510-4. doi: 10.1182/blood-2007-09-114165. Epub 2008 Jun 11.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / toxicity*
  • Antibodies, Monoclonal / toxicity*
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD / blood*
  • Antigens, Differentiation, Myelomonocytic / blood*
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Gemtuzumab
  • Haptoglobins / metabolism
  • Hemoglobins / metabolism*
  • Hemolysis*
  • Humans
  • Infant
  • Leukemia, Myeloid, Acute / complications*
  • Leukemia, Myeloid, Acute / drug therapy
  • Male
  • Receptors, Cell Surface / blood*
  • Receptors, Scavenger
  • Syndrome

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Haptoglobins
  • Hemoglobins
  • Receptors, Cell Surface
  • Receptors, Scavenger
  • haptoglobin-hemoglobin complex
  • Gemtuzumab