Reduced-Intensity Delayed Intensification in Standard-Risk Pediatric Acute Lymphoblastic Leukemia Defined by Undetectable Minimal Residual Disease: Results of an International Randomized Trial (AIEOP-BFM ALL 2000)
Delayed intensification (DI) in acute lymphoblastic leukemia (ALL) is an essential element in treatment protocols but is intensive and associated with toxicity. This study originated from the AIEOP-BFM 2000 trial and aimed at testing non-inferiority of reduction in DI from 49 days (P-II) to 29 days (P-III) with a shorter duration of steroids and lower doses of cyclophosphamide, vincristine, and doxorubicin.
The randomized prospective trial AIEOP-BFM ALL 2000 is a European multinational cohort study. From 2000 to 2006, 4,937 patients were enrolled on the trial. Of 1,346 patients with standard risk criteria (SR, the lowest risk category), 1,164 were randomly assigned on the reduced regimen P-III or the standard regimen P-II (roughly half in each arm).
Median follow-up time was 8.4 years. The disease-free survival was 91.8% vs. 95.8% with the reduced regimen vs. the standard treatment with 62 versus 42 events (p=0.04). 8-year OS was 96.1% versus 98% (NS). Acute toxicity was about the same in the two regimens with slightly more life-threatening events occurring with standard therapy P-II (n=10 vs. 7). The reduced regimen P-III was not associated with similar outcomes compared to the standard regimen P-II and therefore, treatment reduction in SR patients with ALL was not successful in this trial. The only subgroups with similar outcomes were ETV6-RUNX1 positive ALL and patients aged 1 to 6 years.
The results of this trial are specific to the BFM backbone and risk stratification which differs compared to other large international trials.