Minimal Residual Disease in AML: Why Has It Lagged Behind Pediatric ALL?

Paietta, Elisabeth

doi:10.1016/j.clml.2015.02.009

Cited by 4 publications

(1 citation statement)

References 53 publications

(53 reference statements)

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“…MRD monitoring methods include multiparameter flow cytometry (MFC) and polymerase chain reaction (PCR) [ 5 ]. MFC monitoring is critical for AML patients, but AML carries multiple immunophenotypic clones and frequently changes the antigen profile after therapies, which restricts the application of MFC-MRD in AML patients [ 6 ]. PCR is another important method for MRD monitoring, particularly for those with leukemic fusion genes [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation

et al. 2021

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Background Sequential monitoring of Wilms’ tumor gene 1 (WT1) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict relapse in adult acute myeloid leukemia (AML). However, the prognostic role of WT1 in pediatric AML after allo-HSCT is unclear. Thus, we determined to see whether sequential monitoring of WT1 after allo-HSCT could predict relapse in AML children. Methods Pediatric AML patients receiving allo-HSCT from January 21, 2012 to December 20, 2018 at the Peking University Institute of Hematology were included in this study. WT1 expression level was determined by TaqMan-based reverse transcription-polymerase chain reaction. WT1 sequential monitoring was performed 1, 2, 3, 4.5, 6, 9, and 12 months post-transplantation and at 6-month intervals thereafter. The primary end point was relapse. The secondary end points included disease-free survival (DFS), overall survival (OS), and non-relapse mortality (NRM). Kaplan–Meier analysis was used for DFS and OS estimates, while competing risk analysis was used for estimating relapse and NRM. Results Of the 151 consecutive patients included, the median age was 10 years (range, 1–17). The optimal cutoff value of WT1 within 1 year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/104 ABL copies), with a sensitivity of 60% and specificity of 79%. Compared with WT1 expression < 0.8%, WT1 expression ≥0.8% indicated significantly higher 5-year cumulative incidence of relapse (CIR, 35.1% vs. 11.3%; P = 0.001), lower 5-year disease-free survival (DFS, 60.4% vs. 80.8%; P = 0.009), and lower 5-year overall survival (OS, 64.9% vs. 81.6%; P = 0.038) rates. Multivariate analyses showed that WT1 was an independent risk factor for relapse (HR 2.89; 95% confidence interval (CI), 1.25–6.71; P = 0.014). Both the CIR (5-year CIR: 8.3% vs. 11.3%; P = 0.513) and DFS (5-year DFS: 91.7% vs. 80.8%; P = 0.208) were comparable between patients achieving minimal residual disease (MRD) negativity after preemptive interferon-α (IFN-α) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies. Conclusions Sequential monitoring of WT1 could predict relapse in pediatric AML after allo-HSCT. WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.

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Section: Introductionmentioning

confidence: 99%

Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation

et al. 2021

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Minimal Residual Disease in Acute Myeloid Leukemia

Sung

Luger

2017

Curr. Treat. Options in Oncol.

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New technology and improved understanding of the pathogenesis of acute leukemias have allowed for sensitive detection of minimal residual disease (MRD). Despite many years of research demonstrating the prognostic value of MRD, there is no standard of care for measurement of MRD in acute myeloid leukemia. The techniques for assessment are continuing to improve at a rapid pace; however, the benefit of risk-adapted approaches for MRD positive disease remains a major question. This review focuses on recent methodological advances for MRD detection, the role of MRD in prognostication, and current application of the available evidence in guiding therapy decisions.

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