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

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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Myelodysplastic Syndromes
Cytarabine
Acute Myeloid Leukemia
Cyclosporine
Refractory Anemia with Excess of Blasts
Multiple Drug Resistance
fludarabine
gemtuzumab
Survival Rate
Hyperbilirubinemia
Lymphocyte Activation
Disease-Free Survival
Blood Platelets

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes. / Tsimberidou, Apostolia; Estey, Elihu; Cortes, Jorge; Thomas, Deborah; Faderl, Stefan; Verstovsek, Srdan; Garcia-Manero, Guillermo; Keating, Michael; Albitar, Maher; O'Brien, Susan; Kantarjian, Hagop; Giles, Francis.

In: Cancer, Vol. 97, No. 6, 15.03.2003, p. 1481-1487.

Research output: Contribution to journalArticle

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, vol. 97, no. 6, pp. 1481-1487. https://doi.org/10.1002/cncr.11239
Tsimberidou, Apostolia ; Estey, Elihu ; Cortes, Jorge ; Thomas, Deborah ; Faderl, Stefan ; Verstovsek, Srdan ; Garcia-Manero, Guillermo ; Keating, Michael ; Albitar, Maher ; O'Brien, Susan ; Kantarjian, Hagop ; Giles, Francis. / Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes. In: Cancer. 2003 ; Vol. 97, No. 6. pp. 1481-1487.
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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.",
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T1 - Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes

AU - Tsimberidou, Apostolia

AU - Estey, Elihu

AU - Cortes, Jorge

AU - Thomas, Deborah

AU - Faderl, Stefan

AU - Verstovsek, Srdan

AU - Garcia-Manero, Guillermo

AU - Keating, Michael

AU - Albitar, Maher

AU - O'Brien, Susan

AU - Kantarjian, Hagop

AU - Giles, Francis

PY - 2003/3/15

Y1 - 2003/3/15

N2 - 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.

AB - 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.

KW - Acute myelogenous leukemia

KW - Cyclosporine

KW - Cytarabine

KW - Fludarabine

KW - Gemtuzumab (Mylotarg™)

KW - Venoocclusive disease

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