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

Apostolia Tsimberidou, Elihu Estey, Jorge Cortes, Deborah Thomas, Stefan Faderl, Srdan Verstovsek, Guillermo Garcia-Manero, Michael Keating, Maher Albitar, Susan O'Brien, Hagop Kantarjian, Francis Giles

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

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™) (6 mg/m2 intravenously [i.v.] on Day 1); fludarabine and ara-C (15 mg/m2 and 0.5 g/m2, 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.

Original languageEnglish (US)
Pages (from-to)1481-1487
Number of pages7
JournalCancer
Volume97
Issue number6
DOIs
StatePublished - Mar 15 2003
Externally publishedYes

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Keywords

  • Acute myelogenous leukemia
  • Cyclosporine
  • Cytarabine
  • Fludarabine
  • Gemtuzumab (Mylotarg™)
  • Venoocclusive disease

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tsimberidou, A., Estey, E., Cortes, J., Thomas, D., Faderl, S., Verstovsek, S., Garcia-Manero, G., Keating, M., Albitar, M., O'Brien, S., Kantarjian, H., & Giles, F. (2003). Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes. Cancer, 97(6), 1481-1487. https://doi.org/10.1002/cncr.11239