Table 4.

Median TSI50,cont. Values (μmol/L) for MTX and Novel Antifolates and Normalized TSI50,cont. Ratios in Childhood Leukemia Subtypes

Initial c/preB-ALLRelapsed c/preB-ALL (rALL)T-ALL AML
TSI50,cont. (μmol/L)TSI50,cont. (μmol/L) Normalized TSI50,cont. Ratio TSI50,cont. (μmol/L) Normalized TSI50,cont. RatioTSI50,cont. (μmol/L) Normalized TSI50,cont. Ratio
MTX  0.058  0.174-150 3.0 0.080  1.4  0.051  0.88  
TMQ  0.022  0.022 1.0 0.012  0.564-151 0.00464-151 0.214-151 
GW1843U89 0.0017  0.0023  1.44-150 0.0036  2.14-153 0.0021  1.2 
MTA  0.076  0.11  1.5  0.414-151 5.44-151 0.11 1.5 
Raltitrexed  0.0047  0.011 2.3  0.0274-151 5.8 0.0134-150 2.8 
ZD9331  0.017  0.045  2.6 0.060  3.54-151 0.017  1.0 
Initial c/preB-ALLRelapsed c/preB-ALL (rALL)T-ALL AML
TSI50,cont. (μmol/L)TSI50,cont. (μmol/L) Normalized TSI50,cont. Ratio TSI50,cont. (μmol/L) Normalized TSI50,cont. RatioTSI50,cont. (μmol/L) Normalized TSI50,cont. Ratio
MTX  0.058  0.174-150 3.0 0.080  1.4  0.051  0.88  
TMQ  0.022  0.022 1.0 0.012  0.564-151 0.00464-151 0.214-151 
GW1843U89 0.0017  0.0023  1.44-150 0.0036  2.14-153 0.0021  1.2 
MTA  0.076  0.11  1.5  0.414-151 5.44-151 0.11 1.5 
Raltitrexed  0.0047  0.011 2.3  0.0274-151 5.8 0.0134-150 2.8 
ZD9331  0.017  0.045  2.6 0.060  3.54-151 0.017  1.0 

TSI50,cont. values were measured by the in situ TS inhibition assay after 21 hours of continuous drug exposure. Mann-Whitney U test was applied to analyze differences between untreated c/preB-ALL and relapsed c/preB-ALL (rALL), T-ALL, or AML. Normalized TSI50,cont. was calculated as (TSI50,cont. for individual sample)/(median TSI50,cont. for group of c/preB-ALL). Wilcoxon signed ranks test was applied to analyze differences between normalized TSI50,cont. ratios for a novel antifolate and for MTX.

F4-150

P ≤ .01;

F4-151

P ≤ .001;

P ≤ .05;

F4-153

P < .1.