II. Indications

  1. Acute Myelogenous Leukemia (AML)
    1. Gemtuzumab ozogamacin

III. Mechanism

  1. CD33
    1. CD33 is a small Protein on the surface of myeloid cells and Monocyte-Macrophage precursors
    2. CD33 interacts with SHP-1 and SHP-2 Protein kinases for intracellular signaling
  2. CD33 Monoclonal Antibody
    1. Conjugate antibodies that deliver cytotoxic drugs to CD33 positive cancer cells

IV. Medications

  1. Gemtuzumab ozogamacin (Mylotarg)
    1. Conjugated Monoclonal Antibody that delivers the cytotoxic drug calicheamicin to cancer cells
    2. Used in Acute Myelogenous Leukemia (AML)

V. Dosing

  1. See other references for disease specific dosing protocols

VI. Adverse Effects

  1. Hepatotoxicity (FDA black box warning)
    1. Includes hepatic veno-occlusive disease (sinusoidal obstruction)
    2. Increased transaminases, GGT, and Serum Bilirubin
  2. Infusion Reactions (including Anaphylaxis)
  3. Severe Hemorrhage
  4. Other common adverse effects
    1. Gastrointestinal (Nausea, Vomiting, Constipation, decreased appetite)
    2. Headache
    3. Rash
    4. Mucositis

VII. Safety

  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters, Unknown Pregnancy category)
    1. Use reliable Contraception
  3. Monitoring
    1. Liver Function Tests
    2. Complete Blood Count with Platelet Count

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Related Studies

Ontology: CD33 antigen (C0054952)

Definition (MSH) A 67-kDa sialic acid binding lectin that is specific for MYELOID CELLS and MONOCYTE-MACROPHAGE PRECURSOR CELLS. This protein is the smallest siglec subtype and contains a single immunoglobulin C2-set domain. It may play a role in intracellular signaling via its interaction with SHP-1 PROTEIN-TYROSINE PHOSPHATASE and SHP-2 PROTEIN-TYROSINE PHOSPHATASE.
Definition (NCI) Myeloid cell surface antigen CD33 (364 aa, ~40 kDa) is encoded by the human CD33 gene. This protein is involved in the mediation of cell adhesion and the regulation of cell-cell signaling.
Concepts Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129)
MSH D063268
SnomedCT 29735006
LNC LP64430-9, LP68374-5, LP20018-5, MTHU026327, MTHU022274
English CD33 - Cluster of diff ag 33, Cluster of diff antigen 33, CD33 antigen, Myeloid Cell Surface Antigen CD33, Sialic Acid-Binding Ig-Like Lectin 3, Antigen CD33, CD33, gp67, gp67, Glycoprotein, Antigens, CD33, CD33 Antigen, Sialic Acid Binding Ig-like Lectin 3, CD33 Antigens, Sialic Acid Binding Ig like Lectin 3, Antigen, CD33, Glycoprotein gp67, Siglec-3, Sialic Acid Binding Ig-like Lectin 3 [Chemical/Ingredient], CD33 Ag, Lymphocyte antigen CD33, CD33 - Cluster of differentiation antigen 33, Cluster of differentiation antigen 33, Myeloid 9, Lymphocyte antigen CD33 (substance)
Czech glykoprotein gp67, antigen CD33, siglec lektin 3
French CD33, Glycoprotéine gp67, Siglec-3, Lectine-3 de type Ig liant l'acide sialique, Antigène CD33, Protéine Siglec-3, Antigènes CD33, Lectine-3 de type Ig spécifique de l'acide sialique
German Sialinsäure-bindendes Ig-ähnliches Lektin 3, Glykoprotein gp67, Antigene, CD33, CD33 Antigen, Sialinsaeure-bindendes Ig-aehnliches Lektin 3, CD33 Antigene, Siglec-3
Italian Antigeni CD33, Lectina Ig-simile legante l'acido sialico 3, Antigene CD33
Spanish Lectina 3 Similar a Ig de Unión al Ácido Siálico, antígeno linfocitario CD33 (sustancia), antígeno linfocitario CD33
Polish Lektyna Siglec 3, Lektyna Siglec3
Russian IMMUNOGLOBULIN-PODOBNYI LEKTIN 3, SVIAZYVAIUSHCHII SIALOVUIU KISLOTU, ANTIGENY CD33, СИАЛОВУЮ КИСЛОТУ СВЯЗЫВАЮЩИЙ IG-ПОДОБНЫЙ ЛЕКТИН 3, ГЛИКОПРОТЕИН GP67, ИММУНОГЛОБУЛИН-ПОДОБНЫЙ ЛЕКТИН 3, СВЯЗЫВАЮЩИЙ СИАЛОВУЮ КИСЛОТУ, АНТИГЕНЫ CD33, GLIKOPROTEIN GP67, SIALOVUIU KISLOTU SVIAZYVAIUSHCHII IG-PODOBNYI LEKTIN 3
Portuguese Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico, Lectina 3 Semelhante a Ig Ligante de Ácido Siálico

Ontology: Gemtuzumab ozogamicin (C1533699)

Definition (NCI_NCI-GLOSS) A monoclonal antibody combined with a toxic substance that is used to treat certain types of acute myeloid leukemia in older patients and is being studied in the treatment of other types of cancer. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. Mylotarg is a type of antibody-drug conjugate.
Definition (NCI) A recombinant, humanized anti-CD33 monoclonal antibody attached to the cytotoxic antitumor antibiotic calicheamicin. In this conjugate, the antibody binds to and is internalized by tumor cells expressing CD33 antigen (a sialic acid-dependent glycoprotein commonly found on the surface of leukemic blasts), thereby delivering the attached calicheamicin to CD33-expressing tumor cells. Calicheamicin binds to the minor groove of DNA, causing double strand DNA breaks and resulting in inhibition of DNA synthesis. (NCI04)
Definition (PDQ) A recombinant, humanized anti-CD33 monoclonal antibody attached to the cytotoxic antitumor antibiotic calicheamicin. In this conjugate, the antibody binds to and is internalized by tumor cells expressing CD33 antigen (a sialic acid-dependent glycoprotein commonly found on the surface of leukemic blasts), thereby delivering the attached calicheamicin to CD33-expressing tumor cells. Calicheamicin binds to the minor groove of DNA, causing double strand DNA breaks and resulting in inhibition of DNA synthesis. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42868&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42868&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1806" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129)
MSH C406061
SnomedCT 127964000, 386640004
English Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, hP67.6-Calicheamicin, Gemtuzumab ozogamicin, gemtuzumab ozogamicin (medication), gemtuzumab-ozogamicin, Gemtuzumab ozogamicin (product), Gemtuzumab ozogamicin (substance), Gemtuzumab Ozogamicin, gemtuzumab ozogamicin, GEMTUZUMAB OZOGAMICIN
Spanish ozogamicina de gemtuzumab (producto), ozogamicina de Gemtuzumab (sustancia), gemtuzumab ozogamicina (producto), gemtuzumab ozogamicina, ozogamicina de Gemtuzumab, ozogamicina de gemtuzumab, gemtuzumab ozogamicina (sustancia)