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Research Article: Association between hematopoietic recovery indicators and minimal residual disease after induction therapy in newly diagnosed pediatric acute myeloid leukemia

Date Published: 2026-09-22

Abstract:
This study aimed to investigate the relationship between peripheral blood and bone marrow hematopoietic recovery indicators and minimal residual disease (MRD) status following induction chemotherapy in pediatric patients with newly diagnosed acute myeloid leukemia (AML), and to evaluate the early predictive value of these indicators for MRD positivity. Clinical data from 62 pediatric patients with newly diagnosed AML who received standard induction chemotherapy between January 2015 to December 2024 were retrospectively reviewed. Patients were stratified into MRD-negative (MRD < 0.1%, n =?43) and MRD-positive group (MRD???0.1%, n =?19) groups based on post-induction MRD assessment. Hematopoietic recovery parameters, including nadir values and time to recovery of absolute neutrophil count (ANC) and platelet (PLT) count, as well as bone marrow cellularity and granulocytic/megakaryocytic recovery on day 28, were compared between groups. Spearman correlation analysis assessed associations between hematopoietic indicators and MRD levels. Multivariate logistic regression identified independent correlates of MRD positivity. Receiver operating characteristic (ROC) curves with DeLong's test compared predictive performance of individual and combined indicators. Least Absolute Shrinkage and Selection Operator (Lasso) regression with 10-fold cross-validation was used for variable selection. Internal validation was performed using 1000 bootstrap resamples. The two groups were well-balanced in baseline characteristics, with no significant differences. Those in the MRD-positive group had significantly lower ANC and PLT nadirs, and prolonged time to ANC and PLT recovery. On day 28, a higher proportion of patients in the MRD-positive group exhibited hypocellular bone marrow, along with impaired granulocytic and megakaryocytic recovery. Spearman analysis showed that PLT recovery time was strongly positively correlated with MRD levels, while PLT nadir showed a strong negative correlation; both correlations were stronger than those observed for ANC-related indicators. Multivariate logistic regression confirmed that delayed PLT recovery and reduced PLT nadir were independent correlates of MRD positivity. The combination of PLT recovery time and PLT nadir achieved an area under the ROC curve (AUC) of 0.820 (95% CI: 0.724 - 0.916) for predicting MRD positivity, with a sensitivity of 84.37% and specificity of 78.21%, significantly outperforming individual indicators. Bootstrap validation confirmed model stability (AUC?=?0.798, 95% CI: 0.712 - 0.884). Hematopoietic recovery indicators are closely associated with MRD status in pediatric AML following induction therapy. MRD-positive patients exhibit delayed and poor-quality hematopoietic recovery. Delayed PLT recovery and reduced PLT nadir are robust independent correlates of MRD positivity, and their combined use offers a simple, accessible tool for early MRD risk stratification and efficacy assessment, particularly in resource-limited settings.

Introduction:
Acute myeloid leukemia (AML) is a highly aggressive clonal disorder arising from hematopoietic stem and progenitor cells, characterized by uncontrolled proliferation and differentiation arrest of myeloid blasts ( 1 ). Accounting for approximately 15% to 20% of childhood leukemias, AML exhibits greater biological heterogeneity, lower initial remission rates, and higher relapse risk compared with acute lymphoblastic leukemia (ALL), contributing to substantial variability in long-term outcomes ( 2 ). Epidemiological…

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