Prognostic significance of minimal residual disease detected by a simplified flow cytometric assay during remission induction chemotherapy in children with acute lymphoblastic leukemia

Abstract

PurposeOur study attempted to determine the prognostic significance of minimal residual disease (MRD) detected by a simplified flow cytometric assay during induction chemotherapy in children with B-cell acute lymphoblastic leukemia (B-ALL).MethodsA total of 98 patients were newly diagnosed with precursor B-ALL from June 2004 to December 2008 at the Asan Medical Center (Seoul, Korea). Of those, 37 were eligible for flow cytometric MRD study analysis on day 14 of their induction treatment. The flow cytometric MRD assay was based on the expression intensity of CD19/CD10/CD34 or aberrant expression of myeloid antigens by bone marrow nucleated cells.ResultsThirty-five patients (94.6%) had CD19-positive leukemic cells that also expressed CD10 and/or CD34, and 18 (48.6%) had leukemic cells with aberrant expression of myeloid antigens. Seven patients with ≥1% leukemic cells on day 14 had a significantly lower relapse-free survival (RFS) compared to the 30 patients with lower levels (42.9% [18.7%] vs. 92.0% [5.4%], P=0.004). Stratification into 3 MRD groups (≥1%, 0.1-1%, and <0.1%) also showed a statistically significant difference in RFS (42.9% [18.7%] vs. 86.9% [8.7%] vs. 100%, P=0.013). However, the MRD status had no significant influence on overall survival. Multivariate analysis demonstrated that the MRD level on day 14 was an independent prognostic factor with borderline significance.ConclusionAn MRD assay using simplified flow cytometry during induction chemotherapy may help to identify patients with B-ALL who have an excellent outcome and patients who are at higher risk for relapse.

Measurements of treatment response in childhood acute leukemia

“…Nevertheless, some groups base their MRD risk-classification on two time points including end of remission induction and post-consolidation [20, 74]. It is important to stress that measurements of MRD during remission induction therapy can also provide valuable prognostic information, allowing the simultaneous identification of patients with poor or excellent response to initial therapy [12, 18, 19, 75, 76]. In patients with T-lineage ALL, MRD is equally distributed in blood and in bone marrow [13, 77].…”

“…For example, testing MRD at later time points during therapy or off therapy in patients with ALL appears to have little informative value unless supported by a clinical suspicion of relapse, and hence it might be given low priority. In addition, flow cytometric testing during remission induction therapy in patients with B-lineage ALL can be performed with a reduced number of antibodies, further saving costs [89, 90]. …”

Implementation of a simplified flow cytometric assays for minimal residual disease monitoring in childhood acute lymphoblastic leukemia

“…Another study analyzed 37 samples at induction time point and found that seven patients who showed a MRD ≥ 1% had a significantly lower relapse‐free survival (RFS) compared to patients with lower level . In the same study, one patient previous classified as low risk by cytogenetic findings also had a MRD >1% and relapsed, suggesting that MRD finding during treatment should be use to redefine the traditional risk stratification scheme for better treatment choice .…”

Outcome of Reinduction Chemotherapy with a Modified Dose of Idarubicin for Children with Marrow-Relapsed Acute Lymphoblastic Leukemia: Results of the Childhood Acute Lymphoblastic Leukemia (CALL)-0603 Study

“…Our study did not incorporate more sensitive method to detect minimal residual disease (MRD) into the protocol. MRD has been reported to be a significant prognostic factor for both newly diagnosed and relapsed ALL ( 29 30 31 ). A recent study showed that a faster acquisition of MRD negativity was associated with a better outcome in relapsed ALL ( 32 ).…”