FREE AMINO ACIDS IN BLOOD. V 425 
Effects of myleran and dimethylmyleran (patient R. Tap.) 
The effects of the drug on plasma free amino acids of patient R. Tap. are presented 
in Figs. 250-267. The chromatograms were selected for illustrations because the 
patient showed some of the most marked and consistent changes encountered. The 
figures illustrate the findings in two studies of dimethylmyleran, one study of the 
effects of myleran, and one study of the effects of CB 2432. 
The patient first received 40 mg of dimethylmyleran (on 3-21-58) and Fig. 250 
shows the free amino acid levels of plasma 4 days after drug. There were no changes 
from the control levels. A decline in the levels of some free amino acids is evident 
at 7 days (Fig. 251) and at 17 days (Fig. 252). Fig. 253 shows that after 74 days the 
plasma free amino acid levels were near the pretreatment levels. The patient received 
30 mg of dimethylmyleran (on 7-24-58) and there was a prompt decline of the levels 
of most free amino acids one day later (Fig. 254). The general response was similar 
to that after the first injection of the drug, but the fall in free amino acids occurred 
much earlier and was more pronounced. The reduction of plasma free amino acids 
was still evident after 14 and 28 days (Figs. 255, 256). Free amino acid patterns 
similar to the pretreatment patterns were observed after 42 and 61 days (Figs. 257, 
258). The plasma taurine level had returned to near pretreatment levels in contrast 
to the finding at 28 days. Dimethylmyleran produced a marked fall in taurine and 
the taurine level was slow to return to pretreatment levels. 
The patient then received 10 mg of myleran per day for to days (beginning on 
10-21-58). Figs. 259 and 260 show the plasma free amino acid levels 1 and 4 days 
after the complete dose of myleran was given. Note the lower taurine and glutamic 
acid levels in particular in the first sample. By the fourteenth day (Fig. 261) the free 
amino acids were near the control levels and high 28, 42, 49, 69, and 76 days after 
myleran administration. When the white cell count was reduced to the maximum 
extent the free amino acid levels were increased. 
Essentially no changes were observed in the erythrocyte free amino acid levels 
following the course of myleran. There was a small increase in glutathione on the 
fourth day that persisted throughout the course of the study. As observed for dime- 
thylmyleran, there was a total free amino acid decrease in the leukocytes following 
administration of myleran and the lowest point of free amino acids was coincident 
with the lowest leukocyte count. As the leukocyte count returned to pretreatment 
levels the free amino acids of the leukocytes returned toward the control levels. One 
interesting difference between the leukocyte count response and free amino acid 
response following myleran and dimethylmyleran is that both the white cell count 
and the free amino acid levels changed more gradually after myleran. 
On 1-19-59 patient R. Tap. received 20 mg of CB 2432 (an isomer of dimethyl- 
myleran) and Fig. 267 shows the findings in the plasma of the patient 14 days later. 
A marked reduction in the glutamic and aspartic acid levels and taurine can be 
observed. After 21 days (not illustrated) the levels of these three amino acids were 
still low. Taurine was not detectable in plasma. 
CONCLUSIONS 
The cytotoxic drugs of the myleran series depress the leukocyte count and alter the 
free amino acid levels of the blood of patients with chronic granulocytic leukemia. 
References p. 447/448 
