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

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.

Impact of Minimal Residual Disease Detection by Next Generation Flow Cytometry on Outcome of Egyptian Patients with Acute Lymphoblastic Leukemia

“…Regarding the best cutoff values for diagnosing relapsed cases, 0.28% was the best cutoff for differentiating relapsed from non-relapsed cases at EOI and 0.91% at EOC. This is in agreement with Pawinska et al who evaluated MRD at three time points (D15, D33, and D78) and discovered that the 0.1% MRD cut-off was the most discriminatory for entire cases at all-time points evaluated (Pawinska et al,2022). In contrast, Borowitz et al suggested that 0.01% was a better cut-off at end of induction (Borowitz et al,2015).…”

“…It plays an essential role to determine the most precise assessment time point featured by the highest sensitivity to predict relapse at EOI, EOC was demonstrated to be identically significant (AUROC EOI vs. AUROC EOC, 0.924 vs. 0. 958.And this agrees with Pawinska et al who -confirmed that MRD on day 33 end of induction in the BM as the most powerful early predictor of relapse (Pawinska-et al, 2022). Contrarily Conter et al who used MRD (0.1%) at end-consolidation for risk stratification.…”

“…On the other hand, it has been demonstrated to be associated with high cost which is a main drawback for its broad applicability. The proper identification of immunoglobulin and T cell receptor gene rearrangements by quantitative real-time polymerase chain reaction (RT-PCR) has been considered as the best standard of care in terms of ALL management (Pawinska et al, 2022). However, the majority of current treatment strategies use an integral approach, applying both MFC and PCR techniques to evaluate MRD in ALL (Riva et al, 2021).…”