Comparison of cladribine- and fludarabine-based induction chemotherapy in relapsed or refractory acute myeloid leukaemia

Ann Hematol. 2016 Oct;95(11):1777-86. doi: 10.1007/s00277-016-2774-z. Epub 2016 Aug 19.

Abstract

Induction regimens integrating cladribine or fludarabine have shown promising outcomes in relapsed or refractory (R/R) acute myeloid leukaemia (AML). We compared the outcome of a cladribine- versus a fludarabine-based regimen as induction chemotherapy for R/R-AML. We included patients with R/R-AML who were treated with a cladribine- or fludarabine-based chemotherapy between 2006 and 2015. We analysed 120 patients, 65 treated with cladribine and 55 treated with fludarabine. The CR rates were 62.7 and 61.4 % for the cladribine group and fludarabine group, respectively (p = 0.890). Poor prognostic factors included older age, secondary AML, poor cytogenetic risk group, prior induction failure, and short first CR duration. No significant overall survival (OS) or relapse-free survival (RFS) differences were found between the groups (OS, p = 0.213; RFS, p = 0.143). However, in a certain subset, survival outcomes were better with cladribine than with fludarabine, including de novo AML, CR at first induction therapy, and not-poor cytogenetic risk group inclusion without overt chemotherapy-refractoriness. By contrast, secondary AML patients had improved survival outcomes when treated with the fludarabine regimen. After CR, better outcomes were observed when allogeneic stem cell transplantation (SCT) was given as consolidation. In R/R-AML, cladribine- and fludarabine-based combination induction chemotherapy had differential survival outcomes according to disease characteristics. Allogeneic SCT after CR with a purine analogue-based regimen improved long-term outcome in these patients.

Keywords: Acute myeloid leukaemia; Cladribine; Fludarabine; Refractory; Relapsed.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Allografts
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cladribine / administration & dosage
  • Combined Modality Therapy
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Drug Evaluation
  • Drug Resistance, Neoplasm
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Recurrence
  • Retrospective Studies
  • Salvage Therapy*
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Cladribine
  • Vidarabine
  • fludarabine

Supplementary concepts

  • CLAG protocol
  • FLAG protocol