High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group

Leukemia. 2007 Jan;21(1):66-71. doi: 10.1038/sj.leu.2404434. Epub 2006 Oct 19.


Pivotal phase II studies in acute myeloblastic leukemia (AML) patients in first relapse have used gemtuzumab ozogamicin (GO) (Mylotarg) at a dose of 9 mg/m(2) on days 1 and 14. These studies showed a 26% response rate (13% complete remission (CR) and 13% CRp (complete remission with incomplete platelet recovery)) but with high degree of hematological and liver toxicities. Based on in vitro studies showing a re-expression of CD33 antigenic sites on the cell surface of blasts cells after exposure to GO, we hypothesized that fractionated doses of GO may be efficient and better tolerated. Fifty-seven patients with AML in first relapse received GO at a dose of 3 mg/m(2) on days 1, 4 and 7 for one course. Fifteen patients (26%) achieved CR and four (7%) CRp. Remission rate correlated strongly with P-glycoprotein and MRP1 activities. The median relapse-free survival was 11 months, similar for CR or CRp patients. Median duration of neutropenia < 500/microl and thrombocytopenia < 50,000/microl were, respectively, 23 and 21 days. No grade 3 or 4 liver toxicity was observed. No veno-occlusive disease occurred after GO or after hematopoietic stem cell transplantation given after GO in seven patients. Mylotarg administered in fractionated doses demonstrated an excellent efficacy/safety profile.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / blood
  • Adult
  • Aged
  • Aged, 80 and over
  • Aminoglycosides / administration & dosage*
  • Aminoglycosides / adverse effects
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD / blood
  • Antigens, Differentiation, Myelomonocytic / blood
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Disease-Free Survival
  • Drug Administration Schedule
  • Gemtuzumab
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / blood
  • Recurrence
  • Remission Induction
  • Sialic Acid Binding Ig-like Lectin 3


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Aminoglycosides
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antineoplastic Agents
  • CD33 protein, human
  • Multidrug Resistance-Associated Proteins
  • Sialic Acid Binding Ig-like Lectin 3
  • Gemtuzumab
  • multidrug resistance-associated protein 1