Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation
Dao-Xing Deng,
Juan-Juan Wen,
Yi-Fei Cheng,
Xiao-Hui Zhang,
Lan-Ping Xu,
Yu Wang,
Chen-Hua Yan,
Yu-Hong Chen,
Huan Chen,
Wei Han,
Feng-Rong Wang,
Jing-Zhi Wang,
Ya-Zhen Qin,
Kai-Yan Liu,
Xiao-Jun Huang,
Xiao-Su Zhao,
Xiao-Dong Mo
Affiliations
Dao-Xing Deng
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Juan-Juan Wen
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Yi-Fei Cheng
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Xiao-Hui Zhang
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Lan-Ping Xu
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Yu Wang
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Chen-Hua Yan
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Yu-Hong Chen
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Huan Chen
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Wei Han
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Feng-Rong Wang
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Jing-Zhi Wang
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Ya-Zhen Qin
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Kai-Yan Liu
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Xiao-Jun Huang
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Xiao-Su Zhao
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Xiao-Dong Mo
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
Abstract 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.
