Unexpected mortality from the use of E-coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia: a report from the Taiwan Pediatric Oncology Group
Dc. Liang et al., Unexpected mortality from the use of E-coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia: a report from the Taiwan Pediatric Oncology Group, LEUKEMIA, 13(2), 1999, pp. 155-160
The relative efficacy and toxicity of E. coli L-asparaginase and epidoxorub
icin used in remission induction therapy for childhood acute lymphoblastic
leukemia (ALL) were assessed in a randomized trial conducted in Taiwan. All
patients had standard-risk ALL, defined as a leukocyte count < 10 x 10(9)/
l and were aged between 1 and 2 or 7 and 10 years, or a leukocyte count <50
x 10(9)/l and were aged between 2 and 7 years, without evidence of a T cel
l or mature B cell immunophenotype, central nervous system leukemia or expr
ession of two or more myeloid-associated antigens. Ninety-three patients we
re randomized to receive E. coli L-asparaginase at 10 000 IU/m(2) thrice we
ekly for nine doses and 108 to receive epidoxorubicin at 20 mg/m(2) weekly
for two doses during remission induction with daily prednisolone, weekly vi
ncristine and, on day 22, a dose of etoposide plus cytarabine. Patients tre
ated with L-asparaginase had a significantly higher rate of fatal infection
with or without hemorrhage than did those who received epidoxorubicin duri
ng remission induction (six of 93 vs none of 108, P = 0.009), resulting in
a lower rate of complete remission in the former group (93.6 vs 99.1%, P =
0.05). In addition, patients treated with L-asparaginase had a higher frequ
ency of hyperglycemia and hypoalbuminemia. The overall rate of event-free s
urvival was lower in patients treated with L-asparaginase than in other pat
ients (P = 0.06); estimated 3-year rates were 72% (95% confidence interval,
55-89%) and 87.2% (78-96%), respectively. We conclude that L-asparaginase
(Leunase) given at 10 000 IU/m(2) for nine doses was poorly tolerated and r
esulted in excessive toxicity, both through its effects as a single agent a
nd possibly through potentiation of etoposide.