Journal
BONE MARROW TRANSPLANTATION
Volume 50, Issue 7, Pages 939-946Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bmt.2015.58
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Funding
- National Institutes of Health/National Cancer Institute [P01 CA55164-19, P01 CA049639-21, R21 CA137637, CCSG P30 CA016672]
- Paul and Mary Haas Chair in Genetics
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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 mu g/kg daily for 6 days starting on day - 9) plus plerixafor (doses of 0, 80, 160 or 240 mu g/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.
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