4.6 Article

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

Journal

BMC CANCER
Volume 21, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12885-021-08022-0

Keywords

Pediatric; Acute myeloid leukemia; Allogeneic hematopoietic stem cell transplantation; Wilms' tumor gene 1; Relapse

Categories

Funding

  1. CAMS Innovation Fund for Medical Sciences (CIFMS) [2019-I2M-5-034]
  2. National Key Research and Development Program of China [2017YFA0104500]
  3. Innovative Research Groups of the National Natural Science Foundation of China [81621001]
  4. National Natural Science Foundation of China [81930004]
  5. Capital's Funds for Health Improvement and Research [2018-4-4089]

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Sequential monitoring of WT1 after allo-HSCT can predict relapse in pediatric AML, and WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.
BackgroundSequential 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.MethodsPediatric 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 12months 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.ResultsOf the 151 consecutive patients included, the median age was 10years (range, 1-17). The optimal cutoff value of WT1 within 1year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/10(4) 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-alpha (IFN-alpha) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies.ConclusionsSequential 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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