Sequential treatment with FLAG-IDA/treosulfan conditioning regimen for patients with active acute myeloid leukemia

Ann Hematol. 2020 Dec;99(12):2939-2945. doi: 10.1007/s00277-020-04232-x. Epub 2020 Sep 6.

Abstract

Sequential protocols combining salvage chemotherapy with reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (alloHCT) for high-risk acute myeloid leukemia (AML) have been studied more than a decade. Purpose of this retrospective analysis was to evaluate the anti-leukemic efficacy and toxicity of FLAG-IDA protocol (fludarabine, cytarabine, and idarubicin) followed by treosulfan-based conditioning for patients with active AML. From January 2014 to November 2019, a total of 29 active AML patients [median age, 64 years (range, 23-73)] were treated. All patients completed protocol regimen and were transplanted. Five patients (17%) had grade 3-4 toxicities; therefore, treosulfan was substituted with total body irradiation (TBI) non-myeloablative conditioning. Six (20%) patients died within 30 post-transplant days, all from infectious complications. Out of 23 evaluable patients on day 30, 22 (96%) achieved complete hematologic remission with full donor chimerism. Non-relapse mortality (NRM) rates at 1 and 3 years were 22% and 49%, respectively. Median overall survival (OS) was 12 (95% CI, 4-20) months. OS and disease-free survival were 50% and 46% at 1 year and 28% and 17% at 2 years, respectively. Age, gender, disease burden, number of previous lines, and comorbidity score did not predict survival. Sequential strategy combining FLAG-IDA and treosulfan may offer a salvage option for few selected patients with active AML; however, high NRM presents a major obstacle to treatment success. Future efforts should focus on reducing NRM by moderating regimen intensity and by better selection of patients.

Keywords: Allogeneic hematopoietic cell transplantation; Relapsed and refractory AML; Salvage; Sequential.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Busulfan / administration & dosage
  • Busulfan / analogs & derivatives*
  • Cohort Studies
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Humans
  • Idarubicin / administration & dosage
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transplantation Conditioning / methods*
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives*
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • treosulfan
  • Vidarabine
  • Busulfan
  • Idarubicin

Supplementary concepts

  • Ida-FLAG protocol