Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic 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 determine...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-021-08022-0 |
| _version_ | 1818649085706502144 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Dao-Xing Deng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T01:28:43Z |
| format | Article |
| id | doaj.art-553056af3492407bb29ddcb4f94c3f23 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-17T01:28:43Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-553056af3492407bb29ddcb4f94c3f232022-12-21T22:08:39ZengBMCBMC Cancer1471-24072021-03-0121111210.1186/s12885-021-08022-0Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantationDao-Xing Deng0Juan-Juan Wen1Yi-Fei Cheng2Xiao-Hui Zhang3Lan-Ping Xu4Yu Wang5Chen-Hua Yan6Yu-Hong Chen7Huan Chen8Wei Han9Feng-Rong Wang10Jing-Zhi Wang11Ya-Zhen Qin12Kai-Yan Liu13Xiao-Jun Huang14Xiao-Su Zhao15Xiao-Dong Mo16Peking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationPeking 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 TransplantationAbstract 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.https://doi.org/10.1186/s12885-021-08022-0PediatricAcute myeloid leukemiaAllogeneic hematopoietic stem cell transplantationWilms’ tumor gene 1Relapse |
| spellingShingle | 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 Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation BMC Cancer Pediatric Acute myeloid leukemia Allogeneic hematopoietic stem cell transplantation Wilms’ tumor gene 1 Relapse |
| title | Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| title_full | Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| title_fullStr | Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| title_full_unstemmed | Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| title_short | Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| title_sort | wilms tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| topic | Pediatric Acute myeloid leukemia Allogeneic hematopoietic stem cell transplantation Wilms’ tumor gene 1 Relapse |
| url | https://doi.org/10.1186/s12885-021-08022-0 |
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