Reduced Delayed Intensification Impacts Risk of Pediatric ALL Relapse

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Increasing ALL survival rates has led to an increased focus on therapy-related morbidity and mortality improvement.
Increasing ALL survival rates has led to an increased focus on therapy-related morbidity and mortality improvement.

The reduction of delayed intensification (DI) chemotherapy led to increased rates of relapse among pediatric patients with standard-risk acute lymphoblastic leukemia (ALL) compared with standard therapy, according to a study published in the Journal of Clinical Oncology.

Survival rates among patients with ALL have increased with modern advancements in treatment, leading to an increased focus on therapy-related morbidity and mortality improvement. Reducing delayed intensification — a standard and integral part of ALL treatment — is a potential strategy to reduce treatment burden and toxicity in this patient population.


For this study, researchers randomly assigned 1164 pediatric patients with standard-risk ALL (as determined by minimal residual disease assessed by polymerase-chain reaction [PCR-MRD]) to receive experimental reduced-intensity DI (protocol III; P-III) or standard DI (protocol II; P-II). The cumulative dose of dexamethasone was reduced by 30%, and vincristine, doxorubicin, and cyclophosphamide doses were reduced by 50% in P-III compared to P-II. DI was administered in 2 parts: patients received part 1 for P-II and P-III over 29 days and 14 days, respectively, and part 2 was administered over days 36 to 49 compared with days 15 to 28, respectively.

The 8-year rate of disease-free survival (DFS) for patients receiving P-II was 92.3%±1.2% compared with 89.2%±1.3% for patients receiving P-III (P =.04). Patients receiving P-II and P-III at 8 years, respectively, also had cumulative incidence of relapse of 6.4%±1.1% and 8.7%±1.2% (P =.09), and overall survival was 98.0%±0.6% and 96.1%±0.8% (P =.06).


The differences in outcomes for P-II and P-III were observed across all clinical and biologic subgroups in the study, but patients characterized as ETV6-RUNX1-positive and patients aged 1 to 6 years at diagnosis had similar outcomes.

Patients in both protocols shared similar toxicity profiles, and the cumulative incidence rate of secondary malignancies did not differ significantly.

Reducing DI was not found to be noninferior to the current standard and led to higher rates of relapse, but the authors concluded, “[t]he data suggest that treatment reduction is feasible in specific subgroups, which underlines the biologic heterogeneity of this cohort selected according to treatment response.”

Reference

Schrappe M, Bleckmann K, Zimmermann M, et al. 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) [published online November 20, 2017]. J Clin Oncol. doi: 10.1200/JCO.2017.74.4946




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