Cancer Research and Treatment

Original Articles

Pediatric cancer

Outcome of Intensive Therapy for Children with Relapsed Acute Myeloid Leukemia: A Single Institution Korean Study: Jae Wook Lee, Jae Won Yoo, Seongkoo Kim, Pil-Sang Jang, Nack-Gyun Chung, Bin Cho; Cancer Res Treat. 2022;54(4):1230-1239. Published online December 17, 2021; DOI: https://doi.org/10.4143/crt.2021.1011

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Purpose
Approximately 30%-40% of pediatric acute myeloid leukemia (AML) patients relapse. In this study, we analyzed the outcome and prognostic factors of relapsed AML patients who had previously received first-line therapy at our institution.
Materials and Methods
The study group consisted of 50 patients who had been diagnosed with AML from April 2009 to December 2018, and then showed first relapse. Thirty-two of the patients (64%) had previously received allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR).
Results
Forty-five of the patients (90%) received intensive chemotherapy upon diagnosis of relapse, and 76% (34/45) of these patients achieved a second CR. Estimated 5-year overall survival for these 45 patients was 44.9%±7.6%. Time from diagnosis to relapse, extramedullary involvement (EMI) at diagnosis, core binding factor AML, and complex karyotype were significant prognostic factors; in multivariate study, both time from diagnosis to relapse and EMI at diagnosis proved significant. There was no difference in 5-year disease-free survival between patients previously treated with chemotherapy only and those who received HSCT in first CR (52.4%±14.9% vs. 52.6%±11.5%). Of the 19 patients who achieved second CR after previous allogeneic HSCT in first CR and subsequent relapse, 11 were treated with chemotherapy only, and seven survive disease-free.
Conclusion
Intensive therapy allowed for long-term survival in 40%-50% of patients, and 50% of patients who achieved second CR, regardless of prior treatment modalities in first CR. Intensive treatment may allow for salvage of a significant portion of patients with relapsed pediatric AML.

Citations

Citations to this article as recorded by

TREML2 enhances sensitivity of acute myeloid leukemia cells to chemotherapy by inhibiting the NF-κB/CXCL10 pathway
Xin Zhang, Shuheng Yan, Xuehong Zhang, Dan Huang, Jiayin Zhou, Xiaoting Song, Yuchao Hao, Xijia Wang, Jinsong Yan
Blood Science.2025; 7(2): e00223. CrossRef
Diagnosis and Treatment of Pediatric Acute Megakaryoblastic Leukemia with NUP98::KDM5A Rearrangement: Case Report
Hyemin Kang, Suejung Jo, Jae Won Yoo, Seongkoo Kim, Jae Wook Lee, Nack-Gyun Chung, Bin Cho, Chae Yeon Lee, Myungshin Kim
Clinical Pediatric Hematology-Oncology.2024; 31(2): 56. CrossRef

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Hematologic malignancy

Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia: Jae Wook Lee, Seongkoo Kim, Pil-Sang Jang, Nack-Gyun Chung, Bin Cho; Cancer Res Treat. 2021;53(2):567-575. Published online October 8, 2020; DOI: https://doi.org/10.4143/crt.2020.507

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Purpose
Recent cooperative trials in pediatric acute lymphoblastic leukemia (ALL) report long-term event-free survival (EFS) of greater than 80%. In this study, we analyzed the outcome and prognostic factors for patients with precursor B cell ALL (n=405) diagnosed during a 10-year period (2005-2015) at our institution.
Materials and Methods
All patients were treated with a uniform institutional regimen based on four risk groups, except for steroid type; patients diagnosed up till 2008 receiving dexamethasone, while subsequent patients received prednisolone. None of the patients received cranial irradiation in first complete remission.
Results
The 10-year EFS and overall survival was 76.3%±2.3% and 85.1%±1.9%. Ten-year cumulative incidence of relapse, any central nervous system (CNS) relapse and isolated CNS relapse was 20.8%±2.2%, 3.7%±1.1% and 2.5%±0.9% respectively. A comparison of established, good prognosis genetic abnormalities showed that patients with high hyperdiploidy had significantly better EFS than those with ETV6-RUNX1 rearrangement (10-year EFS of 91.2%±3.0% vs. 79.5%±4.4%, p=0.033). For the overall cohort, male sex, infant ALL, initial CNS involvement, and Philadelphia chromosome (+) ALL were significant factors for lower EFS in multivariate study, while high hyperdiploidy conferred favorable outcome. For high and very high risk patients (n=231), high hyperdiploidy was the only significant factor for EFS in multivariate study.
Conclusion
Regarding good prognosis genetic abnormalities, patients with high hyperdiploidy had significantly better outcome than ETV6-RUNX1 (+) patients. High hyperdiploidy was a major, favorable prognostic factor in the overall patient group, as well as the subgroup of patients with higher risk.

Citations

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Diagnostic and therapeutic advances in adults with acute lymphoblastic leukemia in the era of gene analysis and targeted immunotherapy
Jae-Ho Yoon, Seok Lee
The Korean Journal of Internal Medicine.2024; 39(1): 34. CrossRef
The potential role of RNA sequencing in diagnosing unexplained insensitivity to conventional chemotherapy in pediatric patients with B-cell acute lymphoblastic leukemia
Xinyu Li, Zaoli Huang, Liwen Zhu, Weixin Lai, Yunyao Li, Han Chen, Diandian Liu, Junjiu Huang, Dunhua Zhou, Yang Li, Wenjun Weng, Honggui Xu, Luhong Xu, Zhenhua Luo, Jianpei Fang
BMC Medical Genomics.2024;[Epub] CrossRef
Distinct Immunophenotypes in the DNA Index-Based Stratification of Pediatric B-Cell Acute Lymphoblastic Leukemia
Myriam Campos-Aguilar, Wilfrido David Tapia-Sánchez, Alberto Daniel Saucedo-Campos, Carlos Leonardo Duarte-Martínez, Sandra Olivas-Quintero, Almarosa Ruiz-Ochoa, Adolfo Rene Méndez-Cruz, Julia Reyes-Reali, María Isabel Mendoza-Ramos, Rafael Jimenez-Flores
Cancers.2024; 16(21): 3585. CrossRef
The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21)
Agnieszka Kaczmarska, Justyna Derebas, Michalina Pinkosz, Maciej Niedźwiecki, Monika Lejman
Cells.2023; 12(3): 357. CrossRef
Overview on Aneuploidy in Childhood B-Cell Acute Lymphoblastic Leukemia
Kinga Panuciak, Emilia Nowicka, Angelika Mastalerczyk, Joanna Zawitkowska, Maciej Niedźwiecki, Monika Lejman
International Journal of Molecular Sciences.2023; 24(10): 8764. CrossRef
Construction of three‐gene‐based prognostic signature and analysis of immune cells infiltration in children and young adults with B‐acute lymphoblastic leukemia
Chunli Xiang, Jie Wu, Liang Yu
Molecular Genetics & Genomic Medicine.2022;[Epub] CrossRef
Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children’s Leukemia Group
Kun-yin Qiu, Hong-gui Xu, Xue-qun Luo, Hui-rong Mai, Ning Liao, Li-hua Yang, Min-cui Zheng, Wu-qing Wan, Xue-dong Wu, Ri-yang Liu, Qi-wen Chen, Hui-qin Chen, Xiao-fei Sun, Hua Jiang, Xing-jiang Long, Guo-hua Chen, Xin-yu Li, Chang-gang Li, Li-bin Huang, Y
Frontiers in Oncology.2021;[Epub] CrossRef

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Outcome and Prognostic Factors for ETV6/RUNX1 Positive Pediatric Acute Lymphoblastic Leukemia Treated at a Single Institution in Korea: Jae Wook Lee, Seong-koo Kim, Pil-Sang Jang, Nack-Gyun Chung, Dae-Chul Jeong, Myungshin Kim, Bin Cho, Hack-Ki Kim; Cancer Res Treat. 2017;49(2):446-453. Published online August 10, 2016; DOI: https://doi.org/10.4143/crt.2016.211

Abstract PDF Supplementary Material PubReader ePub

Purpose
ETV6/RUNX1 (+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables.
Materials and Methods
Sixty-three patients were diagnosed with ETV6/RUNX1 (+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETV6/RUNX1 (+) fusion, and the presence of additional cytogenetic abnormalities.
Results
The 5-year event-free survival was 84.1±4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9±4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative-polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5±6.9%.
Conclusion
ETV6/RUNX1 ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end ofremission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.

Citations

Citations to this article as recorded by

Genetic Profiling of Acute and Chronic Leukemia via Next-Generation Sequencing: Current Insights and Future Perspectives
Laras Pratiwi, Fawzia Hanum Mashudi, Mukti Citra Ningtyas, Henry Sutanto, Pradana Zaky Romadhon
Hematology Reports.2025; 17(2): 18. CrossRef
Outcome and Prognostic Factors of Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Relapsed or Refractory ETV6/RUNX1-Positive Acute Lymphoblastic Leukemia
Guan-hua Hu, Xiao-hui Zhang, Kai-yan Liu, Lan-ping Xu, Yu Wang, Yi-fei Cheng, Xiao-jun Huang
Acta Haematologica.2024; 147(5): 534. CrossRef
Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia
Jae Wook Lee, Seongkoo Kim, Pil-Sang Jang, Nack-Gyun Chung, Bin Cho
Cancer Research and Treatment.2021; 53(2): 567. CrossRef
Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children’s Leukemia Group
Kun-yin Qiu, Hong-gui Xu, Xue-qun Luo, Hui-rong Mai, Ning Liao, Li-hua Yang, Min-cui Zheng, Wu-qing Wan, Xue-dong Wu, Ri-yang Liu, Qi-wen Chen, Hui-qin Chen, Xiao-fei Sun, Hua Jiang, Xing-jiang Long, Guo-hua Chen, Xin-yu Li, Chang-gang Li, Li-bin Huang, Y
Frontiers in Oncology.2021;[Epub] CrossRef
ETV6/RUNX1-positive childhood acute lymphoblastic leukemia in China: excellent prognosis with improved BFM protocol
Yu Wang, Hui-min Zeng, Le-ping Zhang
Italian Journal of Pediatrics.2018;[Epub] CrossRef
Prognostic factors and treatment of pediatric acute lymphoblastic leukemia
Jae Wook Lee, Bin Cho
Korean Journal of Pediatrics.2017; 60(5): 129. CrossRef
ETV6 and ETV7: Siblings in hematopoiesis and its disruption in disease
Parisa Rasighaemi, Alister C. Ward
Critical Reviews in Oncology/Hematology.2017; 116: 106. CrossRef
Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and mechanisms underlying its relapse
Congcong Sun, Lixian Chang, Xiaofan Zhu
Oncotarget.2017; 8(21): 35445. CrossRef

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