AML refractory to primary induction with Ida-FLAG has a poor clinical outcome

Leuk Res. 2018 May:68:22-28. doi: 10.1016/j.leukres.2018.02.012. Epub 2018 Feb 20.

Abstract

We evaluated outcomes of 100 patients with high risk AML treated with Ida-FLAG induction as first-line therapy. 72 achieved remission with one cycle; 19 did not. High risk cytogenetics and TP53 mutations were associated with failure to achieve remission. In those reaching remission, allogeneic bone marrow transplantation was associated with better relapse-free and overall survival. Those not achieving remission with induction therapy were extremely unlikely to reach remission with further therapy and had a dismal prognosis. Exploratory molecular analysis confirmed persistence of the dominant genetic mutations identified at diagnosis. Ex vivo chemosensitivity did not demonstrate significant differences between responders and non-responders. Thus, Ida-FLAG induction has a high chance of inducing remission in patients with high risk AML. Those achieving remission require allogeneic transplantation to achieve cure; those not achieving remission rarely respond to salvage chemotherapy and have a dismal outcome. Alternatives to conventional chemotherapy must be considered in this group.

Keywords: AML; Chemosensitivity; Chemotherapy; Molecular genetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cytarabine / therapeutic use
  • Female
  • Genes, p53
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Idarubicin / therapeutic use
  • Induction Chemotherapy*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Remission Induction
  • Retrospective Studies
  • Treatment Outcome
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use
  • Young Adult

Substances

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

Supplementary concepts

  • Ida-FLAG protocol

Grants and funding