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

John Magenau, Hiromi Tobai, Attaphol Pawarode, Thomas Braun, Edward Peres, Pavan Reddy, Carrie Kitko, Sung Choi, Gregory Yanik, David Frame, Andrew Harris, Harry Erba, Lisa Kujawski, Kojo Elenitoba-Johnson, Jennifer Sanks, Dawn Jones, Sophie Paczesny, James Ferrara, John Levine, Shin Mineishi

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4258-4264
Number of pages7
JournalBlood
Volume118
Issue number15
DOIs
StatePublished - Oct 13 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Clofarabine and busulfan conditioning facilitates engraftment and provides significant antitumor activity in nonremission hematologic malignancies'. Together they form a unique fingerprint.

  • Cite this

    Magenau, J., Tobai, H., Pawarode, A., Braun, T., Peres, E., Reddy, P., Kitko, C., Choi, S., Yanik, G., Frame, D., Harris, A., Erba, H., Kujawski, L., Elenitoba-Johnson, K., Sanks, J., Jones, D., Paczesny, S., Ferrara, J., Levine, J., & Mineishi, S. (2011). Clofarabine and busulfan conditioning facilitates engraftment and provides significant antitumor activity in nonremission hematologic malignancies. Blood, 118(15), 4258-4264. https://doi.org/10.1182/blood-2011-06-358010