Clofarabine and busulfan conditioning facilitates engraftment and provides significant antitumor activity in nonremission hematologic malignancies

Blood. 2011 Oct 13;118(15):4258-64. doi: 10.1182/blood-2011-06-358010. Epub 2011 Aug 12.

Abstract

Patients with hematologic malignancies not in remission before allogeneic hematopoietic stem cell transplantation (HSCT) have a poor prognosis. To improve the antitumor activity of conditioning, we combined clofarabine with myeloablative doses of busulfan in a phase 1/2 study in nonremission hematologic malignancies. Forty-six patients were enrolled, including 31 patients with nonremission acute myelogenous leukemia (AML). Patients had a median age of 53 years, with a median comorbidity index of 3. Donors were unrelated, HLA mismatched, or both in 59% of patients. Common grade III to IV nonhematologic toxicities included transient transaminitis (50%), mucositis (24%), hand-foot syndrome (13%), transient hypoxia (13%), nausea/vomiting (9%), and diarrhea (9%). All patients engrafted. Complete remission was achieved in 80% of all patients by day +30 and in 100% of AML patients without prior hematopoietic stem cell transplantation. Two-year nonrelapse mortality for all patients was 31%, and overall survival was 28%. In AML, the overall survival was 48% at 1 year and 35% at 2 years. These data suggest that clofarabine combined with myeloablative doses of busulfan is well tolerated, secures engraftment, and possesses significant antitumor activity, particularly in nonremission AML. This study is registered at www.ClinicalTrials.gov under identifier NCT00556452.

Publication types

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

MeSH terms

  • Adenine Nucleotides / administration & dosage*
  • Adenine Nucleotides / adverse effects
  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Arabinonucleosides / administration & dosage*
  • Arabinonucleosides / adverse effects
  • Busulfan / administration & dosage*
  • Busulfan / adverse effects
  • Child, Preschool
  • Clofarabine
  • Disease-Free Survival
  • Graft Survival / drug effects*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant
  • Leukemia / mortality*
  • Leukemia / therapy*
  • Male
  • Middle Aged
  • Myeloablative Agonists / administration & dosage*
  • Myeloablative Agonists / adverse effects
  • Remission Induction
  • Survival Rate
  • Time Factors
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous

Substances

  • Adenine Nucleotides
  • Antineoplastic Agents
  • Arabinonucleosides
  • Myeloablative Agonists
  • Clofarabine
  • Busulfan

Associated data

  • ClinicalTrials.gov/NCT00556452