Go with the Flow—Early Assessment of Measurable Residual Disease in Children with Acute Lymphoblastic Leukemia Treated According to ALL IC-BFM2009

SIMPLE SUMMARY: Monitoring of residual disease is a very important aspect of modern treatment approaches in many types of cancer. In acute leukemias in both children and adults, molecular and cytometric methods are used to assess the burden of leukemia at different points during therapy. Residual disease measured at the end of induction was shown to be the strongest predictor of outcome. Analyzing the outcomes of children with acute lymphoblastic leukemia (ALL), we aimed to establish the most informative cut-off and time point of assessment. Applying only the measurement of residual disease by flow cytometry along with genotypic findings, we managed to identify patients with a poor prognosis. Although new precise, molecular techniques as the next generation sequencing strategy are approaching daily clinical practice, flow cytometry is still a reliable, standardized method of residual disease detection. We may say ‘go with the flow’; thus, the assessment of residual disease by multiparametric flow cytometry is a proper method for the management of ALL patients according to risk-adapted therapies. ABSTRACT: Measurable residual disease (MRD) is a well-known tool for the evaluation of the early response to treatment in patients with acute lymphoblastic leukemia (ALL). In respect to predicting the relapse the most informative cut-off and time point of MRD measurement during therapy were evaluated in our study. Between 1 January 2013 and 31 December 2019, multiparametric flow cytometry (MFC) MRD was measured in the bone marrow of 140 children with ALL treated according to the ALL IC-BFM2009 protocol. The MRD cut-off of 0.1% and day 33, end of induction, were the most discriminatory for all patients. Patients with negative MRD on day 15 and 33 had a higher 5-year overall survival—OS (100%) and a higher relapse-free survival—RFS rate (97.6%) than those with positive levels of MRD (≥0.01%) at both time points (77.8% and 55.6%, p = 0.002 and 0.001, respectively). Most patients with residual disease below 0.1% on day 15 exhibit hyperdiploidy or ETV6-RUNX1 in ALL cells. Measurement of MRD at early time points can be used with simplified genetic analysis to better identify low and high-risk patients, allowing personalized therapies and further improvement in outcomes in pediatric ALL.