402 G. ROUSER et al. 
count was 500 000/mm?’ and fluctuated between 450000 and 600 000 cells/mm? 
during the course of the study. There was no definite change in the leukocyte count 
or any change in clinical status as a result of the administration of the drug. This 
study demonstrates that the free amino acids of plasma and cells may undergo 
marked changes as a result of drug administration without any apparent change in 
the hematological or clinical status of the patient. 
In judging the marked changes produced by nitrogen mustard it is well to keep in 
mind the fact that the changes observed are distinctly different from those produced 
by in vitro incubation of blood of these patients as pointed out in part I. The 7m 
vitvo incubation of blood from chronic lymphatic leukemia patients results in marked 
elevations of the levels of alanine, glutamic acid and aspartic acid in plasma and the 
complete disappearance of glutamine from the blood after several hours. These 
changes are distinctly different from those seen after drug administration. Patients 
without treatment did not show the marked changes observed after the administra- 
tion of nitrogen mustard. 
Effects of chlorambucil on the free amino acids of the blood of humans 
The effects of chlorambucil on blood free amino acids of another patient (W. Ric. 3) 
with chronic lymphatic leukemia are illustrated in Figs. 145-156. Figs. 145-147 
show the plasma, erythrocytes, and leukocytes 1 day after completion of a dose of 
14 mg given at the rate of 2 mg/day (for seven days). Figs. 148-150 show plasma 
and cells 8 days after the total dose was administered, while Figs. 151-153 and 
154-156 show the plasma and cells on the twenty-first and sixty-second days after 
administration of the total dose. In the first post-treatment plasma sample free 
amino acid levels were much lower than for untreated patients. The plasma levels 
of free amino acids were still somewhat lower at the end of the study than were 
most commonly encountered in untreated patients. One of the most marked changes 
was for taurine which was virtually absent from the first post-treatment plasma 
sample and thereafter increased in amount throughout the period of study. 
The erythrocyte free amino acid pool was lower at the first of the study than usually 
seen in untreated patients and remained at a somewhat reduced level throughout 
the course of the study. There were some dramatic effects on the leukocyte free amino 
acid pool. The most marked change was, as for plasma, that of the taurine concen- 
tration. Taurine was reduced to approximately 15°% of the usual leukocyte level. 
Although other free amino acids were also reduced, these reductions were less pro- 
nounced. The most marked reductions aside from that of taurine were the reductions 
of ethanolamine-O-phosphate and glutathione. Throughout the course of the study 
the taurine level remained low, although it did increase in the second sample drawn 
8 days after discontinuation of drug therapy. 
The leukocyte count was 48 000/mmé* prior to taking chlorambucil and dropped to 
30 000/mm? at the end of the week of drug administration. The count then rose 
gradually to 77 000/mm® 35 days after drug had been discontinued and remained at 
this level throughout the course of study. The depression of the leukocyte count was 
associated with a marked reduction in free amino acids of plasma, erythrocytes, and 
leukocytes. At all times the peripheral blood showed a preponderance of lympho- 
cytes (84% of the cells were lymphocytes when the cell count was 30 000/mm* and 
over 90% of the cells were lymphocytes on all other occasions). 
References p. 447/448 
