Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation

M. Konopleva, C. B. Benton, P. F. Thall, Z. Zeng, E. Shpall, S. Ciurea, P. Kebriaei, A. Alousi, U. Popat, P. Anderlini, Y. Nieto, S. Parmar, W. Qiao, J. Chen, G. Rondon, B. McMullin, R. Y. Wang, H. Lu, W. Schober, G. WoodworthA. Gulbis, R. Cool, M. Andreeff, R. Champlin

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day-9) plus plerixafor (doses of 0, 80, 160 or 240 μg/kg daily for 4 days starting on day-7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting. We compared the clinical effects and outcomes of AML/MDS study patients (n=40) with 164 patients from a historical data set who received Bu-Flu alone before allo-SCT by stratifying on cytogenetics and disease status to correct for bias. Study patients had increased myeloid chimerism and lower rates of GvHD. There was no significant difference in relapse-free survival or overall survival. The G-CSF plus plerixafor combination increased circulating WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic cells.

Original languageEnglish (US)
Pages (from-to)939-946
Number of pages8
JournalBone marrow transplantation
Volume50
Issue number7
DOIs
StatePublished - Jul 3 2015

ASJC Scopus subject areas

  • Hematology
  • Transplantation

MD Anderson CCSG core facilities

  • Biostatistics Resource Group
  • Clinical and Translational Research Center
  • Flow Cytometry and Cellular Imaging Facility
  • Clinical Trials Office

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