In 1967, Hill4 and his associates, and
Oettgen,5 first described the induction of
complete remissions. Hill's paper dis
cussed three patients treated with
L-asparaginase prepared from E. coli.
These three patients had acute lymphoblastic leukemia. One of these patients
achieved a complete remission after 32
days of therapy; however, four weeks
after discontinuation of L-asparaginase,
the patient relapsed. Oettgen reported
therapeutic response in four patients
with acute lymphoblastic leukemia and
one with acute myeloblastic leukemia;
however, he had no response in two fur
ther patients with acute myeloblastic
leukemia and two with lymphosarcoma.
Even with the use of the L-asparagin
ase derived from E. coli, supplies were
initially limited and each batch of new material required extensive testing to de
termine not only its activity but also its
potential toxicity. At this time, there was considerable concern regarding its
possible bacterial product contami
nation and many of the initial side ef
fects, especially nausea and vomiting, were attributed to contamination of the
original preparations. After repeated ex
posure to L-asparaginase, some patients
developed sensitization and serious if
not fatal anaphylactic reactions could
occur. It was thought that this sensitiza
tion was possibly due to impurities in the
initial preparations and further purifi
cation has, in fact, modified this risk of
sensitization.
Although the initial hopes that L
asparaginase would occupy a major and
unique role in the treatment of acute leu
kemia have not been forthcoming, it is
still an effective agent in the treatment of some cancers, particularly childhood
acute lymphoblastic leukemia. How
ever, with the use of L-asparaginase in
large doses over a short period of time,
in combination with other known effec
tive chemotherapeutic agents, it has
been possible to prolong the survival of