Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy

Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy
This study aimed to determine the relevance of MRD assessment at two points during induction therapy. The authours postulated that an early MRD at day 19 could identify a subgroup of very good prognosis leukemia. 
This clinical trial was part of the St Jude Total Therapy XV study.
Bone marrow MRD was assessed on days 19 and 46 of induction therapy by flow cytometry, PCR, or both. MRD-based risk classification had 3 levels based on the two time points and not corrected for method of MRD measurement.
A total of 488 children were included in the study.
The mean EFS and OS for global population were respectively 85.8% and 92.5%. MRD level was significantly associated with both EFS, OS and CRR for the global population. Patients with either t(12;21) or hyperdiploid ALL and negative day 19-MRD had particularly good prognosis. A day 19-MRD level >1% was associated with a high mortality rate for the subgroup of T-ALL and NCI standard-risk B-ALL with a respective OS of 68.5% and 76.7%. Day 46-MRD level positivity was predictive of poorer OS and higher risk of relapse for both NCI standard and high-risk B-ALL.
This is a well conducted study with large accrual and long term follow-up allowing the evaluation of 10-year EFS and OS. Philadelphia positive ALL (Ph-ALL) were not included because of the low number (10). The fact that the study did not mandate the method of measuring MRD may have introduced bias.
This study confirmed the relevance of MRD assessment in ALL and the clinical impact of measuring MRD twice in induction. Other groups including COG and AIEOP measure MRD at two time points as well albeit with different chemotherapy backbones. The new very low risk groups identified here may be candidates for therapy reduction. A similar study is already underway in COG (AALL0931).