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Long-Term Disease-Free Survival After Gemtuzumab, Intermediate-Dose Cytarabine, and Mitoxantrone in Patients With CD33 + Primary Resistant or Relapsed Acute Myeloid Leukemia

2008; Lippincott Williams & Wilkins; Volume: 26; Issue: 32 Linguagem: Inglês

10.1200/jco.2007.15.9764

1527-7755

Patrice Chevallier, Jacques Delaunay, Pascal Turlure, Arnaud Pigneux, Mathilde Hunault, Richard Garand, Thierry Guillaume, Hervé Avet‐Loiseau, Nathalia Dmytruk, Stéphane Girault, Nöel Milpied, Norbert Ifrah, Mohamad Mohty, Jean‐Luc Harousseau,

Histone Deacetylase Inhibitors Research

To determine the antitumor activity and safety of a combination of gemtuzumab ozogamicin (GO), intermediate-dose cytarabine, and mitoxantrone (MIDAM) in patients with refractory or relapsed CD33(+) acute myeloid leukemia (AML).We treated 62 patients with refractory (n = 18) or relapsed (n = 44) CD33(+) AML. Median age was 55.5 years. Salvage regimen consisted of GO 9 mg/m(2) on day 4, cytarabine 1 g/m(2) every 12 hours on days 1 through 5, and mitoxantrone 12 mg/m(2)/d on days 1 through 3. Median follow-up time was 26.5 months.Thirty-one patients (50%) achieved complete remission (CR), and eight patients (13%) had CR with delayed platelet recovery (CRp); the overall response (OR; CR + CRp) rate was 63%. A significantly higher OR rate was achieved in patients who had relapsed versus refractory AML (73% v 39%, respectively; P = .007) and patients with CD33 expression more than 98% of the blast population versus less than 98% (79% v 52.3%, respectively; P = .03). The overall, event-free, and disease-free survival rates were 41%, 33%, and 53% at 2 years, respectively. Leukocytosis more than 20,000/microL at MIDAM therapy, high-risk cytogenetics, and absence of postremission therapy were adverse prognostic factors. Age, disease status, and/or CD33 expression did not influence survival parameters. Four early toxic deaths occurred; a grade 3 to 4 hyperbilirubinemia rate of 16% was observed, and two patients had veno-occlusive disease (3%).The MIDAM regimen seems to be an effective salvage regimen for refractory/relapsed CD33(+) AML patients. These encouraging results support the need for a randomized phase III trial before considering this combination of GO and chemotherapy as superior or the standard of care treatment for refractory/relapsed CD33(+) AML patients.