Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes

Cancer. 2003 Mar 15;97(6):1481-7. doi: 10.1002/cncr.11239.


Background: Gemtuzumab is used to treat patients with previously untreated or recurrent acute myelogenous leukemia (AML). The fludarabine and cytarabine (ara-C) regimen is active in these patients. Resistance to gemtuzumab is associated with blast multidrug resistance (MDR). The objectives of this study were to evaluate the efficacy and toxicity of a combination regimen of gemtuzumab, fludarabine, ara-C, and the MDR modifier (cyclosporine [CyA]) in patients with previously untreated AML, refractory anemia with excess blasts (RAEB), or RAEB in transformation (RAEBT).

Methods: The MFAC regimen was comprised of gemtuzumab (Mylotarg trade mark ) (6 mg/m(2) intravenously [i.v.] on Day 1); fludarabine and ara-C (15 mg/m(2) and 0.5 g/m(2), respectively, twice daily on Days 2-6); and CSA (6 mg/kg loading dose before gemtuzumab, followed by 16 mg/kg continuous i.v. infusion on Days 1 and 2).

Results: Fifty-nine evaluable patients were treated: 39 patients (66%) had AML and 20 patients (34%) had RAEB/RAEBT. Their median age was 57 years (range, 27-76 years). The MFAC regimen induced complete remission (CR) in 27 patients (46%) and CR with incomplete platelet recovery (CRp) in 1 patient (2%). The median survival period is 8 months. At 12 months, the survival rate is 38% and the event-free survival rate in patients with CR/CRp is 27%. Infections complicated 38% of the courses of chemotherapy. Grade 3/4 toxicity included hyperbilirubinemia in 31% and transaminitis in 7% of the patients. Four patients (7%) developed hepatic venoocclusive disease (VOD).

Conclusions: The MFAC regimen may merit further study in patients with AML if measures to avoid and/or treat VOD can be incorporated into the regimen.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / analysis
  • Aminoglycosides*
  • Anemia, Refractory, with Excess of Blasts / drug therapy*
  • Anemia, Refractory, with Excess of Blasts / pathology
  • Anti-Bacterial Agents / administration & dosage
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aspartate Aminotransferases / analysis
  • Cyclosporine / administration & dosage
  • Cytarabine / administration & dosage
  • Female
  • Gemtuzumab
  • Humans
  • Hyperbilirubinemia / chemically induced
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Survival
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives*


  • Aminoglycosides
  • Anti-Bacterial Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cytarabine
  • Cyclosporine
  • Gemtuzumab
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Vidarabine
  • fludarabine