422 G. ROUSER, K. KELLY, B. JELINEK, D. HELLER 
samples showed spots from uncharacterized substances in the lower left portion of 
the chromatograms. 
The response of patient R. Tho. to dimethylmyleran demonstrates the repro- 
ducibility of the methods and the relatively small effects produced by dimethyl- 
myleran in lymphatic leukemia. This is in direct contrast to the marked changes in 
both the hematological status and free amino acid levels produced by the same 
amount of drug in patients with chronic granulocytic leukemia. 
The effects of dimethylmyleran in chronic granulocytic leukemia (patient M. Fal.) 
The two studies carried out with patient M. Fal. illustrate a number of the marked 
changes that can be produced by dimethylmyleran and the effects of different amounts 
of drug. Fig. 231 shows the effects on the leukocyte count of two different amounts 
(5 and 20 mg) of dimethylmyleran. On both occasions a marked fall in the leukocyte 
count was observed. Minimal changes were observed in the plasma free amino acids 
MF 2 CHROMIC GRANULOCYTIC LEUKEMIA 
RESPONSE TO DIMETHYLMYLERAN 
200 . 




N \N 
180 \ o15mg/kg \ 0.60mg/kg 
SX 
160 \ N 
% wl \ 
'o 140 \N 
= wt \ 
E \N 
Bs 100 \ 
= 80 \ 
S \ 
g 60 \N \ 
4S 40 \ \ 
N N 
al \N \ 
MAR APR MAY JUN JUL 
Fig. 231. Leukocyte response of M. Fal. (chronic granulocytic leukemia) after dimethylmyleran. 
See Figs. 232-249 for chromatographic results. 
— 
after 5 mg of drug. All free amino acids were increased only on the second day after 
drug administration. The erythrocytes showed a general increase of free amino acids 
with a decrease in glutamic acid at the peak of the white cell response. There was 
also a distinct reduction in the glutathione level on the first day post-treatment with 
a return to the control level in subsequent samples. The marked changes in the leuko- 
cyte free amino acid patterns at the lower dosage level are shown in Figs. 232-237. The 
most striking changes were observed on the second day post-treatment. The leukocyte 
free amino acid pool was reduced to extremely low levels (Fig. 235). The free amino 
acids were at the control level 5 days later. 
Figs. 238-243 show the effects of 20 mg of dimethylmyleran on the leukocyte free 
amino acid pools. Marked shifts in the pool constituents are indicated and were 
most pronounced at 8, 11, and 13 days (Figs. 241-243). The changes consisted of 
marked decreases of most free amino acids with the appearance of two new com- 
pounds (Fig. 241). These changes persisted throughout the time that the leukocyte 
mass was large enough to sample. The glutathione level remained at or somewhat 
Referenses p. 447/448 
