FREE AMINO ACIDS IN BLOOD. III 389 
level was frequently above the highest level seen in normal individuals as noted also 
for patients with chronic granulocytic leukemia. 
One difficulty encountered early in the studies of chronic lymphatic leukemia was 
the marked effect of nitrogen mustard upon the free amino acids of blood and urine. 
Initially, patients who had been treated with small doses of drugs inadequate to 
produce any demonstrable clinical or hematological change were included in the un- 
treated patient category, particularly when the drug had been given several weeks 
prior to the withdrawal of blood for free amino acid studies. It was subsequently 
found that this method of examination was not suitable. The cytotoxic drug frequent- 
ly had marked effects on the free amino acid levels of blood even when there were no 
observable clinical or hematological effects. These changes were evident several 
weeks after even a small dose of nitrogen mustard (see part IV). The failure to 
appreciate this difference accounts for the earlier report from this laboratory? to 
the effect that glutamine might disappear from the blood of chronic lymphatic 
leukemia patients. At this time it was not realized that small amounts of nitrogen 
mustard could produce this change. Subsequently, the effect of the drug was appre- 
ciated®°. 
Leukocyte samples obtained from the blood and bone marrow of some of the pa- 
tients with chronic lymphatic leukemia had very low levels of glutamine without 
any form of treatment. A very low glutamine level is illustrated in Fig. 117. The 
chromatogram was prepared from an extract of leukocytes removed from the bone 
marrow of a patient (A. Sil. 2) with chronic lymphatic leukemia without previous 
treatment. Fig. 118 illustrates the opposite type of finding where more glutamine, as 
well as a large amount of glutathione, is evident in the alcohol extracts of lym- 
phocytes (patient E. Sch. 9). Fig. 119 shows the same extract after treatment with 
hydrogen peroxide to oxidize glutathione completely. Fig. 120 illustrates the presence 
of an intermediate amount of glutamine in the lymphocytes of the same patient on a 
different occasion. Fig. 121 shows the free amino acid pattern of lymphocytes ob- 
tained from still another patient (M. Blo. 3) where the glutamine level was quite 
low. The free amino acids in the leukocytes of this patient with chronic lymphatic 
leukemia resembled to a marked extent the free amino acid pool observed in lym- 
phoblasts from a patient with acute lymphoblastic leukemia (Figs. 130, 131). Fig. 122 
shows the free amino acid pattern of lymphocytes obtained from another patient 
(A. Sil. 2) where glutamine was much higher, and it is to be noted that the free amino 
acid patterns of the lymphocytes from the patients shown in Figs. 121 and 122 are 
different in several respects. Patient M. Blo. shown in Fig. 121 followed a more acute 
clinical course. It is not surprising that the free amino acid levels of leukocytes from 
this patient resembled the pattern seen in the acute lymphoblastic phase to be 
discussed below. 
The plasma glutamine levels in the patients with chronic lymphatic leukemia were 
frequently at, or slightly below, the lower limit seen in the normal individuals, but 
it is not possible to state that plasma glutamine levels are characteristically lower 
than normal in chronic lymphatic leukemia. There appears to be a definite tendency 
toward lower plasma glutamine levels, particularly for patients with the more pro- 
gressive form of the disease. 
Most of the findings in the urine from patients with chronic lymphatic leukemia 
were within the normal range as illustrated in parts IV and VI. Fig. 123 shows an 
References p. 447/448 
