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Late Bone Marrow Relapse Risk Stratification in Pediatric Patients With B-Cell Acute Lymphoblastic Leukemia


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In an analysis of the German ALL-REZ BFM 2002 trial, reported in the Journal of Clinical Oncology, Eckert et al found that postinduction minimal residual disease (MRD)-based treatment stratification resulted in “excellent survival” in pediatric patients with late relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Study Details

The analysis included 413 children and adolescents (median age = 9.7 years at relapse diagnosis; 30 patients aged ≥ 18 years) treated for late bone marrow BCP-ALL relapse diagnosed between January 2002 and December 2015. Patients with MRD of 10−3 or greater at relapse after standard induction therapy were recommended to receive allogeneic hematopoietic stem cell transplantation (HSCT) in second complete remission; those with MRD less than 103 continued to receive consolidation and maintenance chemotherapy (but could receive allogeneic HSCT from a matched sibling donor). MRD was assessed after induction treatment and at intervals during relapse until HSCT.

Key Findings

Event-free survival was good among both patients with favorable response (MRD less than 103) and poor response to induction treatment, with 10-year rates of 72% vs 65% being observed; 10-year overall survival was 82% vs 74%. Patients with MRD of 102 or greater after induction had poorer 10-year event-free survival (56%). 

Early nonresponders—defined as patients with ≥ 25% leukemic blasts after induction—had the poorest prognosis (10-year event-free survival = 22%). Late nonresponders—defined as patients with MRD of 103 or greater before HSCT—had 10-year event-free survival of 50% and 10-year overall survival of 63%. The investigators noted that these outcomes in principle justify use of allogeneic HSCT in such patients.

From a panel of candidate genes, TP53 alterations (present in 8% of patients with available data) were the only alterations with independent prognostic value in MRD-based response subgroups. On multivariate analysis, significantly poorer event-free survival was observed for TP53 loss/alteration (12 of 132 patients) in patients with good response to induction (hazard ratio [HR] = 3.37, P = .004); TP53 loss (4 of 106 patients) in patients with poor response (HR = 4.51, P = .016); and TP53 loss/mutation (20 of 245 patients) in those with good or poor response (HR = 2.51, P = .005).

The investigators concluded, “After induction treatment, MRD-based treatment stratification resulted in excellent survival in patients with late relapsed BCP-ALL. Prognosis could be further improved in very poor responders by intensifying treatment directly after induction. TP53 alterations can be defined as a novel genetic high-risk marker in all MRD response groups in late relapsed BCP-ALL. Here, we identified early and late nonresponders to be considered as events in future trials.”

Cornelia Eckert, PhD, of the Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the German Childhood Cancer Foundation, German Federal Ministry of Education and Research, and others. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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