Control of relapsed or refractory acute myeloid leukemia by clofarabine in preparation for allogeneic stem cell transplant

Leuk Lymphoma. 2015;56(12):3365-9. doi: 10.3109/10428194.2015.1020059. Epub 2015 Sep 24.

Abstract

Allogeneic stem cell transplant is indicated for patients with refractory or relapsed acute myeloid leukemia (AML). Since elimination of the leukemic load is thought to be a prerequisite for treatment success, we here investigate toxicity and anti-leukemic activity of a clofarabine-AraC salvage protocol preceding transplant. In this retrospective analysis, we observed induction of objective remissions in 86% of patients receiving clofarabine-AraC as compared to 83% with sequential high dose AraC/mitoxantrone (S-HAM) and 50% after mitoxantrone/topotecane/AraC (MTC) salvage strategies. In addition, clofarabine conferred anti-leukemic activity to some patients who failed initial MTC or S-HAM therapy. For overall and leukemia-free survival, we identified cytogenetically defined adverse risk markers but not response to therapy to be a strong predictor. In summary, the clofarabine-AraC salvage strategy combines pronounced anti-leukemic activity with an acceptable toxicity profile and allows the majority of patients with relapsed or refractory AML to proceed to allo-SCT, even in cytogenetically defined high risk situations.

Keywords: Allogeneic stem cell transplant; clofarabine; cytarabine; relapsed and refractory AML; salvage therapy.

MeSH terms

  • Adenine Nucleotides / administration & dosage
  • Adenine Nucleotides / therapeutic use*
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Arabinonucleosides / administration & dosage
  • Arabinonucleosides / therapeutic use*
  • Clofarabine
  • Drug Resistance, Neoplasm
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Recurrence
  • Retreatment
  • Retrospective Studies
  • Salvage Therapy
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • Adenine Nucleotides
  • Antimetabolites, Antineoplastic
  • Arabinonucleosides
  • Clofarabine