Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome

Eur J Haematol. 2012 Jan;88(1):52-60. doi: 10.1111/j.1600-0609.2011.01703.x. Epub 2011 Nov 17.

Abstract

The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotides / administration & dosage
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Arabinonucleosides / administration & dosage
  • Clofarabine
  • Cyclosporine / administration & dosage
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Leukemia, Myeloid, Acute / mortality*
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives
  • Myelodysplastic Syndromes / mortality*
  • Myelodysplastic Syndromes / therapy*
  • Retrospective Studies
  • Stem Cell Transplantation*
  • Survival Rate
  • Transplantation Conditioning*
  • Transplantation, Homologous

Substances

  • Adenine Nucleotides
  • Arabinonucleosides
  • Immunosuppressive Agents
  • Cytarabine
  • Clofarabine
  • Cyclosporine
  • Mycophenolic Acid