Effect of protracted high-dose L-asparaginase given as a second exposure in a Berlin-Frankfurt-Munster-based treatment: Results of the randomized 9102 intermediate-risk childhood acute lymphoblastic leukemia study - A reportfrom the Associazione Italiana Ematologia Oncologia Pediatrica

Purpose: To assess in a randomized study the therapeutic effect of the addi tion of high-dose L-asparaginase (HD ASP) in the context of a Berlin-Frankf urt-Munster (BFM)-based chemotherapy regimen for intermediate risk (IR) chi ldhood acute lymphoblastic leukemia (ALL). Patients and Methods: From March 1991 to April 1995, a total of 705 patient s, with 59% of the cohort of patients fewer than 15 years old, with newly d iagnosed non-B ALL, enrolled onto the Associazione Italiana Ematologia Onco logia Pediatrica (AIEOP) ALL-91 study, were assigned to the IR group. Patie nts in remission at the beginning of the reinduction phase were randomized either to the standard treatment (SD ASP arm) or the experimental treatment (HD ASP arm; weekly intramuscular administration of HD ASP 25,000 IU/m(2) repeated for a total of 20 weeks). Most of the patients (90%) were treated with Erwinia chrysanthemi L-asparaginase product. Results: Among the 610 patients randomized to the SD ASP arm (n = 322) or t o the HD ASP arm (n = 288), relapse occurred at a median time of 24 months after randomization in 76 (24%) and in 64 children (22%), respectively. Mos t of the relapses occurred in the marrow (100 isolated, 21 combined). There was no significant difference between the disease-free survival in the two treatment arms (P = .64), with estimated values at 7 years from randomizat ion of 72.4% (SE 3.1) v 75.7% (SE 2.6) in the SD ASP and HD ASP arms, respe ctively. Conclusion: No advantage wets observed for IR ALL children treated with BFM -based intensive chemotherapy who received protracted E chrysanthemi HD ASP during reinduction and the early continuation phase. J Clin Oncol 19:1297- 1303. (C) 2001 by American Society of Clinical Oncology.