Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia

Abstract

The Dana-Farber Cancer Institute (DFCI) Childhood ALL Consortium Protocol 95-01 was designed to minimize therapy-related morbidity for children with newly diagnosed ALL without compromising efficacy. Patients participated in randomized comparisons of (1) doxorubicin given with or without dexrazoxane, a cardioprotectant (high-risk patients), (2) intensive intrathecal chemotherapy and cranial radiation (standard-risk patients), and (3) Erwinia and Escherichia coli asparaginase (all patients). Between 1996 and 2000, 491 patients (aged 0-18 years) were enrolled (272 standard risk and 219 high risk). With a median of 5.7 years of followup, the estimated 5-year event-free survival (EFS) for all patients was 82% ؎ 2%. Dexrazoxane did not have a significant impact on the 5-year EFS of high-risk patients (P ‫؍‬ .99), and there was no significant difference in outcome of standardrisk patients based on type of central nervous system (CNS) treatment (P ‫؍‬ .26).Compared with E coli asparaginase, Erwinia asparaginase was associated with a lower incidence of toxicity (10% versus 24%), but also an inferior 5-year EFS (78% ؎ 4% versus 89% ؎ 3%, P ‫؍‬ .01). We conclude that (1) dexrazoxane does not interfere with the antileukemic effect of doxorubicin, (2) intensive intrathecal chemotherapy is as effective as cranial radiation in preventing CNS relapse in standard-risk patients, and (3) onceweekly Erwinia is less toxic than E coli asparaginase, but also less efficacious.

The utility of performing the initial lumbar puncture on day 8 in remission induction therapy for childhood acute lymphoblastic leukemia: TCCSG L99‐15 study

“…Especially, high-dose MTX, dexamethasone, and intensive use of asparaginase are recognized as valuable components that act not only in the PB and the BM but also in the CSF [2,7,20,[23][24][25]. We employed these components in consecutive studies except the use of dexamethasone in remission induction treatment, because the precedent L95-14 study did not show any superiority of dexamethasone to PSL [12,14,15,18,26].…”

Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation

“…The half-life of Erwinia asparaginase is shorter than other forms of asparaginase, and the shorter half-life of Erwinia asparaginase has demonstrated clinical implications, with the need for more frequent dosing (every 2-3 days). 10,34 When utilized in patients with a history of E. coli asparaginase hypersensitivity reactions, the majority of patients receiving Erwinia asparaginase have been shown to achieve goal nadir asparaginase activity levels. A subsequent allergy to Erwinia asparaginase (in patients who previously developed an allergy to E. coli derived-preparations) has been reported at rates of 3-33%.…”

The coagulopathy and thrombotic risk associated with L-Asparaginase treatment in adults with acute lymphoblastic leukaemia

“…Two large randomised studies have shown superior efficacy for E. coli L-Asp when compared with Erwinia L-Asp in terms of complete remission rate, relapse rate and overall survival, but at the expense of increased toxicity. 19,20 Erwinia L-Asp is often used as a second-or third-line agent in patients developing hypersensitivity to E. coli L-Asp preparations. Erwinia L-Asp has also been linked to thrombosis in the literature but population sizes have been small and doses given often differ from those currently recommended.…”