Table 4.

CEP-701 inhibits engraftment of FLT3/ITD leukemia


Leukemia sample 1, % CD45, sorted

Leukemia sample 9, %CD45
Sorted
Unsorted
Vehicle
CEP-701
Vehicle
CEP-701
Vehicle
CEP-701
3.3   0   96.1   8.7   98.3   50.4  
3.2   0   89.0   74.6   94.2   19.1  
4.7   0   95.5   13.2   92.6   76.9  
4.6   0   95.6   91.2   75.7   11.7  
11.3   0   95.0   86.9   98.0   46.5  
19.4   0   90.2   80.0   90.0   —  
9.3   0   94.7   1.3   —   —  
—   0   95.3   78.2   —   —  
8.0*
 
0*
 
93.9*
 
54.2*
 
91.5*
 
40.9*
 

Leukemia sample 1, % CD45, sorted

Leukemia sample 9, %CD45
Sorted
Unsorted
Vehicle
CEP-701
Vehicle
CEP-701
Vehicle
CEP-701
3.3   0   96.1   8.7   98.3   50.4  
3.2   0   89.0   74.6   94.2   19.1  
4.7   0   95.5   13.2   92.6   76.9  
4.6   0   95.6   91.2   75.7   11.7  
11.3   0   95.0   86.9   98.0   46.5  
19.4   0   90.2   80.0   90.0   —  
9.3   0   94.7   1.3   —   —  
—   0   95.3   78.2   —   —  
8.0*
 
0*
 
93.9*
 
54.2*
 
91.5*
 
40.9*
 

CD34+/CD38 cells (5 × 103) obtained from leukemia sample 1 (Table 1) were injected via tail vein into 2 groups of 10 sublethally irradiated NOD-SCID mice. In a subsequent experiment, 5 × 106 unsorted cells and 5 × 103 CD34+/CD38 cells from leukemia sample 9 were likewise injected into 4 groups of 8 mice. Mice were then treated with CEP-701 (20 mg/kg) or vehicle twice daily for 5 days every 4 weeks. Some of the mice in the different groups died of apparent infection in the first month of the experiment; thus, final numbers range from 5 to 8 for each group. At sacrifice, the bone marrow cells were analyzed by flow cytometry for human CD45 staining. The % CD45 refers to the percentage of the total marrow that stained for human CD45 (as compared with murine CD45).

—indicates the animal died.

*

Indicates the mean value for the mice in that group.

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