The fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) chemotherapy regimen is an alternative to anthracycline-based therapy for the treatment of acute myeloid leukemia for patients with pre-existing cardiac disease

Eur J Haematol. 2016 Nov;97(5):471-478. doi: 10.1111/ejh.12757. Epub 2016 May 3.

Abstract

We conducted a retrospective study assessing FLAG (fludarabine, cytarabine, and granulocyte colony-stimulating factor) as first-line treatment in 56 newly diagnosed acute myeloid leukemia patients considered ineligible for anthracycline-based treatment due to advanced age, significant comorbidities, or pre-existing cardiac disease. The median age was 69 (21-80); 46% received FLAG for pre-existing cardiac disease and others due to age (32%), non-cardiac comorbidities (20%), or previous anthracycline exposure (2%). The induction mortality was 16% and, among evaluable patients, 48% achieved a complete remission after the first induction course with an additional patient achieving a remission after a second course for a total complete remission rate of 50%. Four patients proceeded to an allogeneic stem cell transplant including two with pre-existing cardiac disease. Among non-transplanted patients, the relapse rate (RR) was 47%. When censored at time of stem cell transplant, the median relapse-free survival was 14.7 months. The median overall survival was 9.3 months with 1- and 2-yr survivals of 44% and 22%, respectively. There was no difference in clinical outcomes between patients treated with FLAG for cardiac reasons vs. other reasons. In conclusion, FLAG is a useful alternative to anthracycline-based induction for Acute myeloid leukemia in those with significant comorbidities including pre-existing cardiac disease.

Keywords: FLAG chemotherapy; acute myeloid leukemia; induction.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anthracyclines / administration & dosage
  • Anthracyclines / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Comorbidity
  • Cytarabine / adverse effects
  • Cytarabine / therapeutic use
  • Female
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Heart Diseases / complications*
  • Humans
  • Leukemia, Myeloid, Acute / complications*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Neoplasms, Second Primary
  • Retrospective Studies
  • Treatment Outcome
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use
  • Young Adult

Substances

  • Anthracyclines
  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Vidarabine

Supplementary concepts

  • FLAG protocol