BACKGROUND: The availability of tyrosine kinase inhibitors (TKIs) has 
considerably changed the management of Philadelphia chromosome positive 
leukemia. The BCR-ABL inhibitor imatinib is also known to inhibit the tyrosine 
kinase of the stem cell factor receptor, c-Kit. Nilotinib is 30 times more 
potent than imatinib towards BCR-ABL in vitro. Studies in healthy volunteers and 
patients with chronic myelogenous leukemia or gastrointestinal stromal tumors 
have shown that therapeutic doses of nilotinib deliver drug levels similar to 
those of imatinib. The aim of this study was to compare the inhibitory effects 
of imatinib and nilotinib on proliferation, differentiation, adhesion, migration 
and engraftment capacities of human cord blood CD34(+) cells.
DESIGN AND METHODS: After a 48-hour cell culture with or without TKIs, CFC, 
LTC-IC, migration, adhesion and cell cycle analysis were performed. In a second 
time, the impact of these TKIs on engraftment was assessed in a 
xenotransplantation model using NOD/SCID/IL-2Rγ (null) mice.
RESULTS: TKIs did not affect LTC-IC frequencies despite in vitro inhibition of 
CFC formation due to inhibition of CD34(+) cell cycle entry. Adhesion of CD34(+) 
cells to retronectin was reduced in the presence of either imatinib or nilotinib 
but only at high concentrations. Migration through a SDF-1α gradient was not 
changed by cell culture in the presence of TKIs. Finally, bone marrow 
cellularity and human chimerism were not affected by daily doses of imatinib and 
nilotinib in a xenogenic transplantation model. No significant difference was 
seen between TKIs given the equivalent affinity of imatinib and nilotinib for 
KIT.
CONCLUSIONS: These data suggest that combining non-myeloablative conditioning 
regimen with TKIs starting the day of the transplantation could be safe.