Cancer Research and Treatment

Original Articles

Pediatric cancer

Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group: Kyung Mi Park, Keon Hee Yoo, Seong Koo Kim, Jae Wook Lee, Nack-Gyun Chung, Hee Young Ju, Hong Hoe Koo, Chuhl Joo Lyu, Seung Min Han, Jung Woo Han, Jung Yoon Choi, Kyung Taek Hong, Hyoung Jin Kang, Hee Young Shin, Ho Joon Im, Kyung-Nam Koh, Hyery Kim, Hoon Kook, Hee Jo Baek, Bo Ram Kim, Eu Jeen Yang, Jae Young Lim, Eun Sil Park, Eun Jin Choi, Sang Kyu Park, Jae Min Lee, Ye Jee Shim, Ji Yoon Kim, Ji Kyoung Park, Seom Gim Kong, Young Bae Choi, Bin Cho, Young Tak Lim; Cancer Res Treat. 2022;54(1):269-276. Published online April 20, 2021; DOI: https://doi.org/10.4143/crt.2021.313

Purpose
Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.
Materials and Methods
Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.
Results
Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×10⁹/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×10⁹/L than in those with initial WBC ≥ 10×10⁹/L (p=0.020).
Conclusion
This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Citations

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Management of Acute Promyelocytic Leukemia at Extremes of Age
Sabine Kayser, Shannon E. Conneely
Cancers.2023; 15(14): 3637. CrossRef
Current Challenges of Asian National Children's Cancer Study Groups on Behalf of Asian Pediatric Hematology and Oncology Group
Chi-kong Li, Purna Kurkure, Ramandeep Singh Arora, Bow Wen Chen, Kirill Kirgizov, Yasuhiro Okamoto, Panya Seksarn, Yongmin Tang, Keon Hee Yoo, Bharat Agarwal, Godfrey C.F. Chan, Rashmi Dalvi, Hiroki Hori, Muhammad Saghir Khan, Alice Yu, Akira Nakagawara
JCO Global Oncology.2023;[Epub] CrossRef
Childhood acute promyelocytic leukemia in a pediatric cancer referral center in Baghdad, Iraq. Improved results with ATRA extended consolidation
Anna Maria Testi, Mazin Faisal Al-Jadiry, Hasanein Habeeb Ghali, Samaher Abdulrazzaq Fadhil, Amir Fadhil Al-Darraji, Raghad Majid Al-Saeed, Ahmed Hatem Sabhan, Safaa A. Faraj Al-Badri, Wisan Majeed Abed, Najiha Ahmed Ameen, Ruaa Zaki Al-Tameemi, Arabiya I
Leukemia & Lymphoma.2022; 63(12): 2940. CrossRef
Death due to unsuspected acute myeloid leukaemia: an unusual forensic diagnosis
Lila Krebs-Drouot, Georgia Karpathiou, Virginie Scolan, Carolyne Bidat-Callet, Baptiste Boyer, Michel Péoc’h
Forensic Science, Medicine and Pathology.2022; 19(1): 60. CrossRef
Successful Treatment of Isolated Central Nervous System Relapse with Intrathecal Chemotherapy in an Adolescent with Acute Promyelocytic Leukemia
Haerim Song, Eun Sang Yi
Clinical Pediatric Hematology-Oncology.2022; 29(2): 70. CrossRef

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CNS cancer

Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae: Joo Ho Lee, Keun-Yong Eom, Ji Hoon Phi, Chul-Kee Park, Seung Ki Kim, Byung-Kyu Cho, Tae Min Kim, Dae Seog Heo, Kyung Taek Hong, Jung Yoon Choi, Hyoung Jin Kang, Hee Young Shin, Seung Hong Choi, Soon Tae Lee, Sung Hye Park, Kyu-Chang Wang, Il Han Kim; Cancer Res Treat. 2021;53(4):983-990. Published online January 13, 2021; DOI: https://doi.org/10.4143/crt.2020.1052

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Purpose
We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities.
Materials and Methods
Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months.
Results
The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction.
Conclusion
De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.

Citations

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Optimal treatment approach for intracranial germinoma: a systematic review and meta-analysis
Zhirui Zhou, Jiabing Liu, Qi Yue, Lingxiao Chen, Xiwei Zhang, Xin Lin, Lin Zheng, Enmin Wang, Yang Wang, Ying Mao
BMC Cancer.2025;[Epub] CrossRef
Distribution and failure patterns of primary central nervous system lymphoma related to the hippocampus: implications for hippocampal avoidance irradiation
Hyejo Ryu, Xue Li, Tae Hoon Lee, Tae Min Kim, Seung Hong Choi, Chul-Kee Park, Soon Tae Lee, Sung-Hye Park, Jae-Kyung Won, Bum-Sup Jang, Il Han Kim, Joo Ho Lee
Journal of Neuro-Oncology.2025;[Epub] CrossRef
NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors
Eric Eunshik Kim, Chul-Kee Park, Seung-Ki Kim, Ji Hoon Phi, Sun Ha Paek, Jung Yoon Choi, Hyoung Jin Kang, Joo Ho Lee, Jae Kyung Won, Hongseok Yun, Sung-Hye Park
Acta Neuropathologica Communications.2024;[Epub] CrossRef
Clinical significance of cerebral microbleeds in patients with germinoma who underwent long-term follow-up
Masayuki Kanamori, Shunji Mugikura, Osamu Iizuka, Naoko Mori, Yoshiteru Shimoda, Ichiyo Shibahara, Rei Umezawa, Keiichi Jingu, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Kyoko Suzuki, Hidenori Endo
Journal of Neuro-Oncology.2024; 170(1): 173. CrossRef
Excluding prepontine cistern from whole ventricle radiotherapy target volume in localized germinoma
Hyejo Ryu, Joo Ho Lee
Radiation Oncology Journal.2023; 41(1): 48. CrossRef
Intracranial Germinomas: Diagnosis, Pathogenesis, Clinical Presentation, and Management
Natalia Kremenevski, Michael Buchfelder, Nirjhar Hore
Current Oncology Reports.2023; 25(7): 765. CrossRef
Proton therapy for pediatric diencephalic tumors
Adam J. Grippin, Susan L. McGovern
Frontiers in Oncology.2023;[Epub] CrossRef
Intracranial Germinoma—Association between Delayed Diagnosis, Altered Clinical Manifestations, and Prognosis
Iwona Jabłońska, Marcin Goławski, Elżbieta Nowicka, Katarzyna Drosik-Rutowicz, Anna Trybus, Rafał Tarnawski, Marcin Miszczyk
Cancers.2023; 15(10): 2789. CrossRef
Outcomes of intracranial germinoma—A retrospective multinational Asian study on effect of clinical presentation and differential treatment strategies
Kyung-Nam Koh, Ru Xin Wong, Dong-Eun Lee, Jung Woo Han, Hwa Kyung Byun, Hong In Yoon, Dong-Seok Kim, Chuhl Joo Lyu, Hyoung Jin Kang, Kyung Taek Hong, Joo Ho Lee, Il Han Kim, Ji Hoon Phi, Seung-Ki Kim, Tai-Tong Wong, Hsin-Lun Lee, I-Chun Lai, Yu-Mei Kang,
Neuro-Oncology.2022; 24(8): 1389. CrossRef
Photon versus proton whole ventricular radiotherapy for non‐germinomatous germ cell tumors: A report from the Children's Oncology Group
David Y. Mak, Zain Siddiqui, Zhihui Amy Liu, Hitesh Dama, Shannon M. MacDonald, Shengjie Wu, Erin S. Murphy, Matthew D. Hall, Victor Malkov, Arzu Onar‐Thomas, Sameera Ahmed, Girish Dhall, Derek S. Tsang
Pediatric Blood & Cancer.2022;[Epub] CrossRef
Factors Influencing Craniospinal Relapse of Intracranial Germinoma After Complete Remission
Takao Tsurubuchi, Kei Hara, Shingo Takano, Ai Muroi, Hiroko Fukushima, Masashi Mizumoto, Noriaki Sakamoto, Masahide Matsuda, Hiroyoshi Akutsu, Hideyuki Sakurai, Eiichi Ishikawa
World Neurosurgery.2022; 166: e325. CrossRef
Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma
Cristina Ilcus, Horatiu Silaghi, Carmen Emanuela Georgescu, Carmen Georgiu, Anca Ileana Ciurea, Simona Delia Nicoara, Cristina Alina Silaghi
Journal of Personalized Medicine.2021; 11(7): 661. CrossRef

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Pediatric cancer

Effectiveness and Safety of Clofarabine Monotherapy or Combination Treatment in Relapsed/Refractory Childhood Acute Lymphoblastic Leukemia: A Pragmatic, Non-interventional Study in Korea: Jung Yoon Choi, Che Ry Hong, Kyung Taek Hong, Hyoung Jin Kang, Seongkoo Kim, Jae Wook Lee, Pil Sang Jang, Nack-Gyun Chung, Bin Cho, Hyery Kim, Kyung-Nam Koh, Ho Joon Im, Jong Jin Seo, Seung Min Hahn, Jung Woo Han, Chuhl Joo Lyu, Eu Jeen Yang, Young Tak Lim, Keon Hee Yoo, Hong Hoe Koo, Hoon Kook, In Sang Jeon, Hana Cho, Hee Young Shin; Cancer Res Treat. 2021;53(4):1184-1194. Published online January 4, 2021; DOI: https://doi.org/10.4143/crt.2020.289

Abstract PDF Supplementary Material PubReader ePub

Purpose
Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development.
Materials and Methods
In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed.
Results
Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events.
Conclusion
Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.

Citations

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Revolutionizing cancer treatment: ROS-induced apoptosis via nanoformulated alkaloids
Swathi Putta, Santhosh Kumar Chinnaiyan, Ramadevi Korni, Venkata Radha Gadela
Journal of Drug Delivery Science and Technology.2025; 104: 106556. CrossRef
Proteomic analysis reveals chromatin remodeling as a potential therapeutical target in neuroblastoma
Zan Liu, Zitong Zhao, Longlong Xie, Zhenghui Xiao, Ming Li, Yong Li, Ting Luo
Journal of Translational Medicine.2025;[Epub] CrossRef
3′-O-β-Glucosylation of nucleoside analogues using a promiscuous bacterial glycosyltransferase
Jonathan P. Dolan, Tessa Keenan, Aisling Ní Cheallaigh, Martin A. Fascione, Gavin J. Miller
RSC Chemical Biology.2025;[Epub] CrossRef
Opciones para el tratamiento de la recaída en leucemia linfoblástica aguda. Revisión de tema
Christian Omar Ramos-Peñafiel, Carlos Martínez-Murillo, Daniela Pérez-Sámano, Camila Terreros-Palacios, Adán Germán Gallardo-Rodríguez, Irma Olarte-Carrillo, Adolfo Martínez-Tovar
Revista Médicas UIS.2024;[Epub] CrossRef
Clofarabine

Reactions Weekly.2023; 1958(1): 155. CrossRef
Patient-Level Meta-analysis of Clofarabine in Acute Lymphoblastic Leukemia
Sima Jeha, Hiroaki Goto, André Baruchel, Emmanuelle Boëlle-Le Corfec, Christine Geffriaud-Ricouard, Rob Pieters, Hee Young Shin
Advances in Therapy.2023; 40(12): 5447. CrossRef
Novel Treatments for Pediatric Relapsed or Refractory Acute B-Cell Lineage Lymphoblastic Leukemia: Precision Medicine Era
Shang Mengxuan, Zhou Fen, Jin Runming
Frontiers in Pediatrics.2022;[Epub] CrossRef

8,333 View
200 Download
4 Web of Science
7 Crossref

Central nervous system

Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years: Meerim Park, Jung Woo Han, Seung Min Hahn, Jun Ah Lee, Joo-Young Kim, Sang Hoon Shin, Dong-Seok Kim, Hong In Yoon, Kyung Taek Hong, Jung Yoon Choi, Hyoung Jin Kang, Hee Young Shin, Ji Hoon Phi, Seung-Ki Kim, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Do Hoon Lim, Hyung Jin Shin, Hyery Kim, Kyung-Nam Koh, Ho Joon Im, Seung Do Ahn, Young-Shin Ra, Hee-Jo Baek, Hoon Kook, Tae-Young Jung, Hyoung Soo Choi, Chae-Yong Kim, Hyeon Jin Park, Chuhl Joo Lyu; Cancer Res Treat. 2021;53(2):378-388. Published online October 28, 2020; DOI: https://doi.org/10.4143/crt.2020.756

Abstract PDF PubReader ePub

Purpose
Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive malignancy with peak incidence in children aged less than 3 years. Standard treatment for central nervous system ATRT in children under the age of 3 years have not been established yet. The objective of this study was to analyze characteristics and clinical outcomes of ATRT in children aged less than 3 years.
Materials and Methods
A search of medical records from seven centers was performed between January 2005 and December 2016.
Results
Forty-three patients were enrolled. With a median follow-up of 90 months, 27 patients (64.3%) showed at least one episode of disease progression (PD). The first date of PD was at 160 days after diagnosis. The 1- and 3-year progression-free survivals (PFS) were 51.2% and 28.5%, respectively. The 1- and 3-year overall survivals were 61.9% and 38.1%, respectively. The 3-year PFS was improved from 0% in pre-2011 to 47.4% in post-2011. Excluding one patient who did not receive any further therapy after surgery, 27 patients died due to PD (n=21), treatment-related toxicity (n=5), or unknown cause (n=1). In univariate analysis, factors associated with higher 3-year PFS were no metastases, diagnosis after 2011, early adjuvant radiotherapy, and high-dose chemotherapy (HDCT). In multivariate analysis, the use of HDCT and adjuvant radiotherapy remained significant prognostic factors for PFS (both p < 0.01).
Conclusion
Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years.

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Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors
Marjolein M.G. Kes, Francisco Morales-Rodriguez, Esther A. Zaal, Terezinha de Souza, Natalie Proost, Marieke van de Ven, Marry M. van den Heuvel-Eibrink, Jeroen W.A. Jansen, Celia R. Berkers, Jarno Drost
Cell Reports Medicine.2025; 6(1): 101878. CrossRef
High-throughput screening of FDA-approved drugs identifies colchicine as a potential therapeutic agent for atypical teratoid/rhabdoid tumors (AT/RTs)
Phongthon Kanjanasirirat, Kedchin Jearawuttanakul, Sawinee Seemakhan, Suparerk Borwornpinyo, Patompon Wongtrakoongate, Suradej Hongeng, Sitthivut Charoensutthivarakul
RSC Advances.2025; 15(16): 12331. CrossRef
Supratentorial ATRT in a young Infant: Expanding the diagnostic spectrum beyond medulloblastoma
Ali Msheik, Mohamad Aoun, Youssef Fares
Interdisciplinary Neurosurgery.2024; 35: 101857. CrossRef
Radiation Therapy Plays an Important Role in the Treatment of Atypical Teratoid/Rhabdoid Tumors: Analysis of the EU-RHAB Cohorts and Their Precursors
Sabine Frisch, Hanna Libuschewski, Sarah Peters, Joachim Gerß, Katja von Hoff, Rolf-Dieter Kortmann, Karolina Nemes, Stefan Rutkowski, Martin Hasselblatt, Torsten Pietsch, Michael C. Frühwald, Beate Timmermann
International Journal of Radiation Oncology*Biology*Physics.2024; 119(4): 1147. CrossRef
An adult with recurrent atypical teratoid rhabdoid tumor of the spine
Antoinette J Charles, Vanessa L Smith, C Rory Goodwin, Margaret O Johnson
CNS Oncology.2024;[Epub] CrossRef
Dynamic Survival Risk Prognostic Model and Genomic Landscape for Atypical Teratoid/Rhabdoid Tumors: A Population-Based, Real-World Study
Sihao Chen, Yi He, Jiao Liu, Ruixin Wu, Menglei Wang, Aishun Jin
Cancers.2024; 16(5): 1059. CrossRef
ESTRO-SIOPE guideline: Clinical management of radiotherapy in atypical teratoid/rhabdoid tumors (AT/RTs)
Beate Timmermann, Claire Alapetite, Karin Dieckmann, Rolf-Dieter Kortmann, Yasmin Lassen-Ramshad, John H. Maduro, Monica Ramos Albiac, Umberto Ricardi, Damien C. Weber
Radiotherapy and Oncology.2024; 196: 110227. CrossRef
Development and epigenetic regulation of Atypical teratoid/rhabdoid tumors in the context of cell-of-origin and halted cell differentiation
Laura Huhtala, Goktug Karabiyik, Kirsi J Rautajoki
Neuro-Oncology Advances.2024;[Epub] CrossRef
Comparative treatment results of children with atypical teratoid/rhabdoid tumor of the central nervous system in the younger age group
L. V. Olkhova, O. G. Zheludkova, L. S. Zubarovskaya, A. S. Levashov, A. Yu. Smirnova, Yu. V. Dinikina, Yu. V. Kushel, A. G. Melikyan, S. K. Gorelyshev, M. V. Ryzhova, Yu. Yu. Trunin, A. G. Gevorgyan, O. B. Polushkina, V. E. Popov, L. P. Privalova, N. B. Y
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Chi-kong Li, Purna Kurkure, Ramandeep Singh Arora, Bow Wen Chen, Kirill Kirgizov, Yasuhiro Okamoto, Panya Seksarn, Yongmin Tang, Keon Hee Yoo, Bharat Agarwal, Godfrey C.F. Chan, Rashmi Dalvi, Hiroki Hori, Muhammad Saghir Khan, Alice Yu, Akira Nakagawara
JCO Global Oncology.2023;[Epub] CrossRef
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Tae-Hwan Park, Seung-Ki Kim, Ji Hoon Phi, Chul-Kee Park, Yong Hwy Kim, Sun Ha Paek, Chang-Hyun Lee, Sung-Hye Park, Eun Jung Koh
Brain Tumor Research and Treatment.2023; 11(4): 254. CrossRef
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Yen-Lin Liu, Min-Lan Tsai, Chang-I Chen, Noi Yar, Ching-Wen Tsai, Hsin-Lun Lee, Chia-Chun Kuo, Wan-Ling Ho, Kevin Li-Chun Hsieh, Sung-Hui Tseng, James S. Miser, Chia-Yau Chang, Hsi Chang, Wen-Chang Huang, Tai-Tong Wong, Alexander T. H. Wu, Yu-Chun Yen
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Vismaya S. Bachu, Pavan Shah, Adrian E. Jimenez, Adham M. Khalafallah, Jignesh Tailor, Debraj Mukherjee, Alan R. Cohen
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Risk Factor Analysis for Secondary Malignancy in Dexrazoxane-Treated Pediatric Cancer Patients: Hyery Kim, Hyoung Jin Kang, Kyung Duk Park, Kyung-Nam Koh, Ho Joon Im, Jong Jin Seo, Jae Wook Lee, Nack-Gyun Chung, Bin Cho, Hack Ki Kim, Jae Min Lee, Jeong Ok Hah, Jun Ah Lee, Young Ho Lee, Sang Kyu Park, Hee Jo Baek, Hoon Kook, Ji Yoon Kim, Heung Sik Kim, Hwang Min Kim, Hee Won Chueh, Meerim Park, Hoi Soo Yoon, Mee Jeong Lee, Hyoung Soo Choi, Hyo Seop Ahn, Yoshifumi Kawano, Ji Won Park, Seokyung Hahn, Hee Young Shin; Cancer Res Treat. 2019;51(1):357-367. Published online May 14, 2018; DOI: https://doi.org/10.4143/crt.2017.457

Abstract PDF Supplementary Material PubReader ePub

Purpose
Dexrazoxane has been used as an effective cardioprotector against anthracycline cardiotoxicity. This study intended to analyze cardioprotective efficacy and secondary malignancy development, and elucidate risk factors for secondary malignancies in dexrazoxane-treated pediatric patients.
Materials and Methods
Data was collected from 15 hospitals in Korea. Patients who received any anthracyclines, and completed treatment without stem cell transplantation were included. For efficacy evaluation, the incidence of cardiac events and cardiac event-free survival rates were compared. Data about risk factors of secondary malignancies were collected.
Results
Data of total 1,453 cases were analyzed; dexrazoxane with every anthracyclines group (D group, 1,035 patients) and no dexrazoxane group (non-D group, 418 patients). Incidence of the reported cardiac events was not statistically different between two groups; however, the cardiac event-free survival rate of patients with more than 400 mg/m² of anthracyclines was significantly higher in D group (91.2% vs. 80.1%, p=0.04). The 6-year cumulative incidence of secondary malignancy was not different between both groups after considering follow-up duration difference (non-D, 0.52%±0.37%; D, 0.60%±0.28%; p=0.55). The most influential risk factor for secondary malignancy was the duration of anthracycline administration according to multivariate analysis.
Conclusion
Dexrazoxane had an efficacy in lowering cardiac event-free survival rates in patients with higher cumulative anthracyclines. As a result of multivariate analysis for assessing risk factors of secondary malignancy, the occurrence of secondary malignancy was not related to dexrazoxane administration.

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Veronika Keresteš, Jan Kubeš, Lenka Applová, Petra Kollárová, Olga Lenčová-Popelová, Iuliia Melnikova, Galina Karabanovich, Mushtaq M Khazeem, Hana Bavlovič-Piskáčková, Petra Štěrbová-Kovaříková, Caroline A Austin, Jaroslav Roh, Martin Štěrba, Tomáš Šimůn
Toxicological Sciences.2024; 198(2): 288. CrossRef
Circ-0006332 stimulates cardiomyocyte pyroptosis via the miR-143/TLR2 axis to promote doxorubicin-induced cardiac damage
Ping Zhang, Yuanyuan Liu, Yuliang Zhan, Pengtao Zou, Xinyong Cai, Yanmei Chen, Liang Shao
Epigenetics.2024;[Epub] CrossRef
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Xiaomeng Liu, Shuping Ge, Aijun Zhang
Children.2024; 11(7): 884. CrossRef
Efficacy of Dexrazoxane in Cardiac Protection in Pediatric Patients Treated With Anthracyclines
Parya Rahimi, Behsheed Barootkoob, Ahmed ElHashash, Arun Nair
Cureus.2023;[Epub] CrossRef
Inducing a Proinflammatory Response with Bioengineered Yeast Vacuoles with TLR2-Binding Peptides (VacT2BP) as a Drug Carrier for Daunorubicin Delivery
Wooil Choi, Woo-Ri Shin, Yang-Hoon Kim, Jiho Min
ACS Applied Materials & Interfaces.2023; 15(35): 41258. CrossRef
Circulating Biomarkers for Monitoring Chemotherapy-Induced Cardiotoxicity in Children
Luigia Meo, Maria Savarese, Carmen Munno, Peppino Mirabelli, Pia Ragno, Ornella Leone, Mariaevelina Alfieri
Pharmaceutics.2023; 15(12): 2712. CrossRef
Hyperhomocysteinemia as a Link of Chemotherapy-Related Endothelium Impairment
Ashot Avagimyan
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Late health outcomes after dexrazoxane treatment: A report from the Children's Oncology Group
Eric J. Chow, Richard Aplenc, Lynda M. Vrooman, David R. Doody, Yuan‐Shung V. Huang, Sanjeev Aggarwal, Saro H. Armenian, K. Scott Baker, Smita Bhatia, Louis S. Constine, David R. Freyer, Lisa M. Kopp, Wendy M. Leisenring, Barbara L. Asselin, Cindy L. Schw
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Primary cardioprotection with dexrazoxane in patients with childhood cancer who are expected to receive anthracyclines: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group
Esmée C de Baat, Elvira C van Dalen, Renée L Mulder, Melissa M Hudson, Matthew J Ehrhardt, Frederike K Engels, Elizabeth A M Feijen, Heynric B Grotenhuis, Jan M Leerink, Livia Kapusta, Gertjan J L Kaspers, Remy Merkx, Luc Mertens, Roderick Skinner, Wim J
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Adriana Linares Ballesteros, Roy Sanguino Lobo, Juan Camilo Villada Valencia, Oscar Arévalo Leal, Diana Constanza Plazas Hernández, Nelson Aponte Barrios, Iván Perdomo Ramírez
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Valentina K. Todorova, Eric R. Siegel, Yihong Kaufmann, Asangi Kumarapeli, Aaron Owen, Jeanne Y. Wei, Issam Makhoul, V. Suzanne Klimberg
Translational Oncology.2020; 13(2): 471. CrossRef
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Petra Kollárová-Brázdová, Anna Jirkovská, Galina Karabanovich, Zuzana Pokorná, Hana Bavlovič Piskáčková, Eduard Jirkovský, Jan Kubeš, Olga Lenčová-Popelová, Yvona Mazurová, Michaela Adamcová, Veronika Skalická, Petra Štěrbová-Kovaříková, Jaroslav Roh, Tom
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Anthracyclines/cyclophosphamide/etoposide

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Sarju Ganatra, Anju Nohria, Sachin Shah, John D. Groarke, Ajay Sharma, David Venesy, Richard Patten, Krishna Gunturu, Corrine Zarwan, Tomas G. Neilan, Ana Barac, Salim S. Hayek, Sourbha Dani, Shantanu Solanki, Syed Saad Mahmood, Steven E. Lipshultz
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Strategies to prevent anthracycline-induced cardiotoxicity in cancer survivors
Neha Bansal, M. Jacob Adams, Sarju Ganatra, Steven D. Colan, Sanjeev Aggarwal, Rudolf Steiner, Shahnawaz Amdani, Emma R. Lipshultz, Steven E. Lipshultz
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Cardiovascular safety of oncologic agents: a double-edged sword even in the era of targeted therapies – Part 2
Antonis A. Manolis, Theodora A. Manolis, Dimitri P. Mikhailidis, Antonis S. Manolis
Expert Opinion on Drug Safety.2018; 17(9): 893. CrossRef

10,449 View
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18 Crossref

APEX1 Polymorphism and Mercaptopurine-Related Early Onset Neutropenia in Pediatric Acute Lymphoblastic Leukemia: Hyery Kim, Heewon Seo, Yoomi Park, Byung-Joo Min, Myung-Eui Seo, Kyung Duk Park, Hee Young Shin, Ju Han Kim, Hyoung Jin Kang; Cancer Res Treat. 2018;50(3):823-834. Published online September 4, 2017; DOI: https://doi.org/10.4143/crt.2017.351

Abstract PDF Supplementary Material PubReader ePub

Purpose
Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL). To improve treatment outcomes, constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. We performed two-stage analyses to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients.
Materials and Methods
Targeted sequencing of 40 patients who exhibited definite MP intolerance was conducted using a novel panel of 211 pharmacogenetic-related genes, and subsequent analysis was performed with 185 patients.
Results
Using bioinformatics tools and genetic data, four functionally interesting variants were selected (ABCC4, APEX1, CYP1A1, and CYP4F2). Including four variants, 23 variants in 12 genes potentially linked to MP adverse reactions were selected as final candidates for subsequent analysis in 185 patients. Ultimately, a variant allele in APEX1 rs2307486was found to be strongly associated with MP-induced neutropenia that occurred within 28 days of initiating MP (odds ratio, 3.44; p=0.02). Moreover, the cumulative incidence of MP-related neutropenia was significantly higher in patients with APEX1 rs2307486 variants, as GG genotypes were associated with the highest cumulative incidence (p < 0.01). NUDT15 rs116855232 variants were strongly associated with a higher cumulative incidence of neutropenia (p < 0.01), and a lower median dose of tolerated MP throughout maintenance treatment (p < 0.01).
Conclusion
We have identified that APEX1 rs2307486 variants conferred an increased risk of MP-related early onset neutropenia. APEX1 and NUDT15 both contribute to cell protection from DNA damage or misincorporation, so alleles that impair the function of either gene may affect MP sensitivities, thereby inducing MP-related neutropenia.

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Parallel Toxicities: A Comparative Analysis of Chemotherapy-Induced Neutropenia and Alopecia
Simonetta I. Gaumond, Karen J. Lee, Peyton V. Warp, Isabella Kamholtz, Emilee M. Dreifus, Joaquin J. Jimenez
Cancers.2025; 17(7): 1163. CrossRef
Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response
Ashwin Kamath, Suresh Kumar Srinivasamurthy, Mukta N. Chowta, Sheetal D. Ullal, Youssef Daali, Uppugunduri S. Chakradhara Rao
Pharmaceuticals.2022; 15(8): 990. CrossRef
The Effect of NUDT15, TPMT, APEX1, and ITPA Genetic Variations on Mercaptopurine Treatment of Pediatric Acute Lymphoblastic Leukemia
Jae Min Lee, Ye Jee Shim, Do-Hoon Kim, Nani Jung, Jung-Sook Ha
Children.2021; 8(3): 224. CrossRef
Interplay between IL6 and CRIM1 in thiopurine intolerance due to hematological toxicity in leukemic patients with wild-type NUDT15 and TPMT
Hyery Kim, Seungwon You, Yoomi Park, Jung Yoon Choi, Youngeun Ma, Kyung Tak Hong, Kyung-Nam Koh, Sunmin Yun, Kye Hwa Lee, Hee Young Shin, Suehyun Lee, Keon Hee Yoo, Ho Joon Im, Hyoung Jin Kang, Ju Han Kim
Scientific Reports.2021;[Epub] CrossRef
NUDT15 polymorphism in healthy children with Bai nationality in Yunnan of China
Gangling Pu, Yali Wang, Shaoqin Duan, Jingpei Chen, Chunhui Yang, Tingting Cui, Chunlian Fang, Yan Zhou, Han Zhang, Xin Tian
Pediatrics International.2021; 63(7): 790. CrossRef
A Dual Face of APE1 in the Maintenance of Genetic Stability in Monocytes: An Overview of the Current Status and Future Perspectives
Gabriela Betlej, Ewelina Bator, Antoni Pyrkosz, Aleksandra Kwiatkowska
Genes.2020; 11(6): 643. CrossRef
Homozygote CRIM1 variant is associated with thiopurine-induced neutropenia in leukemic patients with both wildtype NUDT15 and TPMT
Yoomi Park, Hyery Kim, Heewon Seo, Jung Yoon Choi, Youngeun Ma, Sunmin Yun, Byung-Joo Min, Myung-Eui Seo, Keon Hee Yoo, Hyoung Jin Kang, Ho Joon Im, Ju Han Kim
Journal of Translational Medicine.2020;[Epub] CrossRef
Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology
Emma C. Bernsen, Melanie M. Hagleitner, Theodorus W. Kouwenberg, Lidwien M. Hanff
Frontiers in Pharmacology.2020;[Epub] CrossRef
Long-term treatment outcomes of children and adolescents with lymphoblastic lymphoma treated with various regimens: a single-center analysis
Ho Jung Choi, Juhee Shin, Sunghan Kang, Jin Kyung Suh, Hyery Kim, Kyung-Nam Koh, Ho Joon Im
BLOOD RESEARCH.2020; 55(4): 262. CrossRef
NUDT15 Variants Cause Hematopoietic Toxicity with Low 6-TGN Levels in Children with Acute Lymphoblastic Leukemia
Eun Sang Yi, Young Bae Choi, Rihwa Choi, Na Hee Lee, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, Hong Hoe Koo
Cancer Research and Treatment.2018; 50(3): 872. CrossRef

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10 Crossref

ALK Protein Expression Is Related to Neuroblastoma Aggressiveness But Is Not Independent Prognostic Factor: Ji Won Lee, Sung Hye Park, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn; Cancer Res Treat. 2018;50(2):495-505. Published online May 22, 2017; DOI: https://doi.org/10.4143/crt.2016.577

Abstract PDF PubReader ePub

Purpose
In this study, anaplastic lymphoma kinase (ALK) mutation and amplification, ALK protein expression, loss of the nuclear alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein, and telomerase reverse transcriptase (TERT) protein expressionwere studied to investigate potential correlations between these molecular characteristics and clinical features or outcomes in neuroblastoma.
Materials and Methods
Seventy-two patients were enrolled in this study. Polymerase chain reaction amplification and direct sequencing were used for mutation analysis. ALK and MYCN amplifications were detected by fluorescence in situ hybridization. Protein expressionwas evaluated by immunohistochemical (IHC) staining.
Results
ALK mutation was found in only two patients (4.1%); ALK amplification was not detected. ALK positivity, loss of nuclear ATRX protein, TERT positivity by IHC were detected in 40 (55.6%), nine (13.0%), and 42 (59.2%) patients, respectively. The incidence of ALK expression increased in accordance with increasing tumor stage (p=0.001) and risk group (p < 0.001). The relapse rate was significantly higher in ALK⁺ patients compared to that of other patients (47.5% vs. 11.3%, p=0.007). However, there was no significant difference in relapse rate when the survival analysis was confined to the high-risk patients.
Conclusion
Although ALK mutation was rare and no amplification was observed, ALK protein expression was found in a significant number of patients and was correlated with advanced stage and high-risk neuroblastoma. ALK protein expression could be considered as a marker related to the aggressive neuroblastoma, but it was not the independent prognostic factor for the outcome.

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Immunohistochemical expression of anaplastic lymphoma kinase in neuroblastoma and its relations with some clinical and histopathological features
Thu Dang Anh Phan, Thao Quyen Nguyen, Nhi Thuy To, Thien Ly Thanh, Dat Quoc Ngo
Journal of Pathology and Translational Medicine.2024; 58(1): 29. CrossRef
Multi-omics revealed that ELAVL3 regulates MYCN in neuroblastoma via immunogenic cell death: Risk stratification and experimental research
Peng Hong, Zaihong Hu, Jie Lin, Kongkong Cui, Zhiqiang Gao, Xiaomao Tian, Qinlin Shi, Tao Lin, Guanghui Wei
International Journal of Biological Macromolecules.2024; 282: 137045. CrossRef
Prominent Staining of MYCN Immunohistochemistry Predicts a Poor Prognosis in MYCN Non-Amplified Neuroblastoma
Manli Zhao, Weizhong Gu, Fei Liu, Lihua Yu, Yan Shu, Lei Liu, Jiahui Hu, Yang Liu, Hongfeng Tang, Jianhua Mao
Pediatric and Developmental Pathology.2023; 26(2): 124. CrossRef
ALKGene Mutation and ALK Protein Expression in Advanced Neuroblastoma and the Potential Value in Risk Stratification in Fine-Needle Aspiration Biopsy Samples
Neha Bhardwaj, Manish Rohilla, Upasana Gautam, Amita Trehan, Deepak Bansal, Nandita Kakkar, Radhika Srinivasan
American Journal of Clinical Pathology.2023;[Epub] CrossRef
Rapid detection of telomerase expression of neuroblastoma in paraffin-embedded tissue: combination of in situ hybridisation and quantitative PCR
Manli Zhao, Zhonghai Guan, Liang Gong, Fei Liu, Weizhong Gu, Lei Liu, Kewen Jiang, Jiabin Cai, Chunyue Feng, Chik Hong Kuick, Kenneth Tou En Chang, Jinhu Wang, Hongfeng Tang, Minzhi Yin, Jianhua Mao
Pathology.2023; 55(7): 958. CrossRef
Interactions of Butyrylcholinesterase with Neuroblastoma-associated Oncoproteins
Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter
Current Enzyme Inhibition.2023; 19(2): 109. CrossRef
Combined Detection of Copy Number Variations of MYCN and ALK using Droplet Digital Polymerase Chain Reaction to Identify High-Risk Patients with Neuroblastoma
Trupti Trivedi, Kinjal Panchal, Neha Bhalala, Priti Trivedi, Harsha Panchal
World Neurosurgery.2022; 159: e48. CrossRef
ALK expression, prognostic significance, and its association with MYCN expression in MYCN non-amplified neuroblastoma
Dinesh Babu Somasundaram, Sheeja Aravindan, Nandita Gupta, Zhongxin Yu, Ashley Baker, Natarajan Aravindan
World Journal of Pediatrics.2022; 18(4): 285. CrossRef
Multifarious Functions of Butyrylcholinesterase in Neuroblastoma: Impact of BCHE Deletion on the Neuroblastoma Growth In Vitro and In Vivo
Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter
Journal of Pediatric Hematology/Oncology.2022; 44(6): 293. CrossRef
Differential Impact of ALK Mutations in Neuroblastoma
Tara O'Donohue, Nitya Gulati, Audrey Mauguen, Brian H. Kushner, Neerav Shukla, M. I. Rodriguez-Sanchez, Nancy Bouvier, Stephen Roberts, Ellen Basu, Nai-Kong Cheung, Shakeel Modak
JCO Precision Oncology.2021; (5): 492. CrossRef
The challenge of defining “ultra‐high‐risk” neuroblastoma
Daniel A. Morgenstern, Rochelle Bagatell, Susan L. Cohn, Michael D. Hogarty, John M. Maris, Lucas Moreno, Julie R. Park, Andrew D. Pearson, Gudrun Schleiermacher, Dominique Valteau‐Couanet, Wendy B. London, Meredith S. Irwin
Pediatric Blood & Cancer.2019;[Epub] CrossRef
ALK in Neuroblastoma: Biological and Therapeutic Implications
Ricky Trigg, Suzanne Turner
Cancers.2018; 10(4): 113. CrossRef

10,131 View
364 Download
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12 Crossref

Incidence and Survival of Childhood Cancer in Korea: Hyeon Jin Park, Eun-Kyeong Moon, Ju Young Yoon, Chang-Mo Oh, Kyu-Won Jung, Byung Kiu Park, Hee Young Shin, Young-Joo Won; Cancer Res Treat. 2016;48(3):869-882. Published online January 21, 2016; DOI: https://doi.org/10.4143/crt.2015.290

Abstract PDF PubReader ePub

Purpose
An epidemiologic study of childhood cancer would provide useful information on cancer etiology and development of management guidelines.
Materials and Methods
Data from the Korea National Cancer Incidence Database were used to examine the incidence and survival of cancer in patients aged 0-14 years. Patients were grouped according to the International Classification of Childhood Cancer, 3rd edition. Age-specific and age-standardized incidences per million and estimated annual percentage change (APC) were calculated by sex and age. Five-year relative survival was calculated for four periods from 1993 to 2011.
Results
The study comprised 15,113 patients with malignant neoplasms. Age-standardized incidence rates for all cancers were 134.9 per million children in 1999-2011 and 144.0 and 124.9 per million for males and females, respectively (M/F ratio, 1.2; p < 0.05). The highest incidences were observed for ‘leukemias, myeloproliferative diseases, and myelodysplastic diseases’ (group I) (46.4), ‘central nervous system neoplasms’ (group III) (18.3), and ‘lymphomas and reticuloendothelial neoplasms’ (group II) (13.4). Age-standardized incidence increased from 117.9 in 1999 to 155.3 in 2011, with an APC of 2.4% (95% confidence interval, 2.1 to 2.7). There was a significant increase of APC in ‘neuroblastoma and other peripheral nervous cell tumors’ (group IV) (5.6%) and ‘other malignant epithelial neoplasms and malignant melanomas’ (group XI) (5.6%). The 5-year relative survival rate for all childhood cancers improved significantly from 56.2% (1993-1995) to 78.2% (2007-2011) (males, 56.7% to 77.7%; females, 55.5% to 78.8%).
Conclusion
This study provides reliable information on incidence and survival trends for childhood cancer in Korea.

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Extra-cranial Malignant Rhabdoid Tumor in Children: A Single Institute Experience: Che Ry Hong, Hyoung Jin Kang, Hee Young Ju, Ji Won Lee, Hyery Kim, Sung-Hye Park, Il Han Kim, Kyung Duk Park, Hee Young Shin; Cancer Res Treat. 2015;47(4):889-896. Published online January 2, 2015; DOI: https://doi.org/10.4143/crt.2013.176

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Purpose
Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor that affects young children. Due to its extreme rarity, most of the available data are based on retrospective case series. To add to the current knowledge of this disease, we reviewed the patients treated for extra-cranial MRT in our institute. Materials and Methods A retrospective medical record review was conducted on children treated for pathologically confirmed extra-cranial MRT at Seoul National University Children’s Hospital between January 2003 and May 2013. Results Eleven patients (7 boys, 4 girls) were diagnosed with extra-cranial MRT at a median age of 9 months old. INI1 staining was important in the pathological confirmation. Six patients (55%) had renal MRT and five (45%) had soft tissue MRT. Five patients (45%) had metastases at diagnosis. All patients underwent chemotherapy, eight patients (73%) underwent surgery, six patients (55%) received therapeutic radiotherapy, and four patients (36%) underwent high dose chemotherapy with autologous stem cell rescue (HDCT/ASCR) with melphalan, etoposide, and carboplatin. Five patients (45%) died of disease following progression (n=3) or relapse (n=2), however, there was no treatment related mortality. The overall survival of the cohort was 53.0% and the event-free survival was 54.5% with a median follow-up duration of 17.8 months (range, 2.3 to 112.3 months). Conclusion Extra-cranial MRT is still a highly aggressive tumor in young children. However, the improved survival of our cohort is promising and HDCT/ASCR with melphalan, etoposide, and carboplatin may be a promising treatment option.

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Clinical Outcome of Relapsed or Refractory Burkitt Lymphoma and Mature B-Cell Lymphoblastic Leukemia in Children and Adolescents: Hyery Kim, Eun Sil Park, Soo Hyun Lee, Hong Hoe Koo, Hyo Sun Kim, Chuhl Joo Lyu, So Eun Jun, Young Tak Lim, Hee Jo Baek, Hoon Kook, Ji Won Lee, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyeo Seop Ahn; Cancer Res Treat. 2014;46(4):358-365. Published online July 21, 2014; DOI: https://doi.org/10.4143/crt.2013.047

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Purpose
Despite the rapid improvement in survival rate from Burkitt lymphoma and mature B-cell lymphoblastic leukemia (B-ALL) in children, a small subset of patients do not respond to first-line chemotherapy or experience relapse (RL). Herein, we report the clinical characteristics and outcomes of these patients.
Materials and Methods
RL or refractory Burkitt lymphoma and mature B-ALL in 125 patients diagnosed from 1990 to 2009 were retrospectively analyzed.
Results
Nineteen patients experienced RL or progressive disease (PD). Among them, 12 patients had PD or RL less than six months after initial treatment and seven had late RL. Seven patients achieved complete response (CR), 11 had PD, and one had no more therapy. Six patients who achieved CR survived without evidence of disease and four of them underwent high-dose chemotherapy (HDC) followed by stem cell transplantation (SCT). However, 11 patients who failed to obtain CR eventually died of their disease. Five-year overall survival (OS) was 31.6±10.7%. OS of patients with late RL was superior to that of patients with early RL (57.1±18.7%, vs. 16.7±10.8%, p=0.014). Achievement of CR after reinduction had significant OS (p < 0.001). OS for patients who were transplanted was superior (p < 0.01). In multivariate analysis, achievement of CR after reinduction chemotherapy showed an association with improved OS (p=0.05).
Conclusion
Late RL and chemotherapy-sensitive patients have the chance to achieve continuous CR using HDC/SCT, whereas patients who are refractory to retrieval therapy have poor prognosis. Therefore, novel salvage strategy is required for improvement of survival for this small set of patients.

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T. T. Valiev, A. A. Khachatryan, S. V. Goryacheva, N. A. Batmanova, K. I. Kirgizov, S. R. Varfolomeeva
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Cristina López, Birgit Burkhardt, John K. C. Chan, Lorenzo Leoncini, Sam M. Mbulaiteye, Martin D. Ogwang, Jackson Orem, Rosemary Rochford, Mark Roschewski, Reiner Siebert
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Clinical Characteristics and Treatment Results of Pediatric Osteosarcoma: The Role of High Dose Chemotherapy with Autologous Stem Cell Transplantation: Ji Won Lee, Hyery Kim, Hyoung Jin Kang, Han-Soo Kim, Sung-Hye Park, In-One Kim, Hyo Seop Ahn, Hee Young Shin; Cancer Res Treat. 2008;40(4):172-177. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.172

Abstract PDF PubReader ePub

Purpose

In this study, we investigated the clinical characteristics and treatment results of osteosarcoma during the past 7 years, and evaluated the role of high dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT).

Materials and Methods

We retrospectively analyzed the clinical data of patients who were diagnosed as osteosarcoma at our center from January, 2000 to December, 2007.

Results

The 5-year overall survival and event-free survival of the patients were 72.6% and 55.9%, respectively. Seventeen (41.5%) patients showed disease progression during treatment or relapse after the end of treatment. The patients who had metastasis at diagnosis or who had a lower grade of necrosis after neoadjuvant chemotherapy showed decreased overall and event-free survival. Four patients received ASCT after HDCT, and 3 of them are alive without disease.

Conclusions

The patients who relapsed or had refractory osteosarcoma or who had metastasis at diagnosis or a lower grade of necrosis after neoadjuvant chemotherapy showed poor prognosis. HDCT with ASCT could be an alternative treatment option for these patients.

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High‐dose chemotherapy followed by autologous stem cell transplantation in pediatric patients with relapsed osteosarcoma
Sung Han Kang, Wanlim Kim, Jong Seok Lee, Jin Kyung Suh, Hyery Kim, Dong Kwan Kim, Se Hoon Choi, Hee Won Cho, Hee Young Ju, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Sung Wook Seo, Ho Joon Im, Ji Won Lee, Kyung‐Nam Koh
Pediatric Blood & Cancer.2023;[Epub] CrossRef
Favorable outcome of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with nonmetastatic osteosarcoma and low-degree necrosis
Kyung Taek Hong, Hyun Jin Park, Bo Kyung Kim, Hong Yul An, Jung Yoon Choi, Jung-Eun Cheon, Sung-Hye Park, Han-Soo Kim, Hyoung Jin Kang
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High-dose chemotherapy and autologous stem cell transplantation with melphalan, etoposide and carboplatin for high-risk osteosarcoma
C R Hong, H J Kang, M S Kim, H Y Ju, J W Lee, H Kim, H-S Kim, S-H Park, K D Park, J D Park, H Y Shin, H S Ahn
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LY294002 suppresses the malignant phenotype and sensitizes osteosarcoma cells to pirarubicin chemotherapy
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Clinical Results of Chemotherapy based Treatment in Retinoblastoma Patients: A Single Center Experience: Hyery Kim, Ji Won Lee, Hyoung Jin Kang, Hyeon Jin Park, Yoon Yi Kim, Hee Young Shin, Young Suk Yu, Il Han Kim, Hyo Seop Ahn; Cancer Res Treat. 2008;40(4):164-171. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.164

Abstract PDF PubReader ePub

Purpose

Retinoblastoma is the most common intraocular malignancy in children. Since the 1990s, chemotherapy was indicated for intraocluar disease to reduce the frequency of enucleation and spare the complications associated with external beam radiation. In this study, we analyzed treatment results of retinoblastoma in our institute.

Materials and Methods

Datas from children diagnosed with retinoblastoma and treated at Seoul National University Children's Hospital between 1986 and 2008 were analyzed retrospectively. We utilized cyclophosphamide, vincristine, adriamycin, and methotrexate (CVAM) for OPD-based adjuvant chemotherapy. From 1990, primary chemotherapy was administered to patients with intraocular disease for eyeball-saving and patients received a combination of etoposide, vincristine, cisplatin (or ifosfamide) as a moderately intensive regimen, or a combination of cisplatin, doxorubicin, etoposide, and cycophosphamide (CDEC) as a highly intensive regimen.

Results

One hundred eighteen children were analyzed. There were 68 unilateral and 50 bilateral diseases. The median age at diagnosis was 1 year and Reese-Ellsworth stage V was the most common stage at the time of diagnosis. All patients were treated by chemotherapy-based multimodality methods, and primary chemotherapy was administered to 80 patients. The 10-year overall and event-free survival rate of all patients were 93.9% and 91.6%, respectively. Two patients who died were in the CDEC regimen group, but there was no significant statistical difference in survival rates by chemotherapy regimens. Fifty-six of 114 eyeballs were saved after primary chemotherapy-based treatment, and the eyeball-saving rate was 49.1%. Six patients relapsed after enucleation and 2 patients were treated successfully after autologous PBSCT. Osteosarcoma occurred in 2 patients as a secondary malignancy, and facial asymmetry after radiotherapy was the most common long-term sequelae.

Conclusions

In this study, the overall and event-free survival rates of retinoblastoma were satisfactory and eye-saving was possible with primary chemotherapy. Development of new chemotherapeutic regimens and a team approach are necessary to improve the eyeball-saving rate.

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Initial Response to Treatment was Highly Associated with the Prognosis of Childhood Rhabdomyosarcoma: A Retrospective Analysis of a Single Center Experience in Korea: Jeong A Park, Eun Kyung Kim, Hyoung Jin Kang, Hee Young Shin, Il Han Kim, Hyo Seop Ahn; Cancer Res Treat. 2008;40(3):111-115. Published online September 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.3.111

Abstract PDF PubReader ePub

Purpose

Following the introduction of a multimodal approach to diagnosis and treatment, the prognosis of rhabdomyosarcoma (RMS) has markedly improved over the last three decades. However, there are few data on treatment outcomes in Korean patients.

Materials and Methods

We performed a retrospective analysis of 77 patients with RMS diagnosed and treated at Seoul National University Children's Hospital between 1986 and 2005.

Results

The overall 5-year survival and event-free survival rates for all patients were 77% and 59%, respectively. The Intergroup Rhabdomyosarcoma Study clinical grouping and initial response to treatment (20-week response) were important prognostic factors.

Conclusions

The outcome of childhood RMS was closely associated with the initial staging and the initial response to treatment. Modulating therapies according to initial responses and risk factors is critical, and new treatment strategies for high-risk patients are needed.

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Case Report

Carboxypeptidase-G2 Rescue in a Patient with High Dose Methotrexate-induced Nephrotoxicity: Eun Sil Park, Kyung Hee Han, Hyoung Soo Choi, Hee Young Shin, Hyo Seop Ahn; Cancer Res Treat. 2005;37(2):133-135. Published online April 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.2.133

Abstract PDF PubReader ePub

A 13 year-old girl with osteosarcoma and pulmonary tumor recurrence developed acute renal failure following high dose methotrexate (12 g/m²) therapy, she had previously tolerated high dose methotrexate and her renal and hepatic functions were normal. Briefly, 48 hours after beginning methotrexate infusion her methotrexate concentration and creatinine level were 1338.8 µM/L and 5.8 mg/dl, respectively. Grade IV oral mucositis and neutropenia with fever developed at 144 hours after MTX infusion. Hydration and alkalinization were continued and leucovorin rescue was intensified based on the plasma MTX concentrations. Plasma exchange was performed twice and hemodialysis 3 times without problems, but methotraxate and creatinine levels remained high, 91.9 µM/L, and 2.5 mg/dl, respectively. After 3 courses of hemodialysis carboxypeptidase-G2 (CPDG2) was administered at 50 U/kg, intravenously over 5 minutes. After 15 minutes of CPDG2 (Voraxaze™) infusion, her plasma MTX concentration was 0.91 µM/L and no rebound elevation or side effects developed. Thirteen days post-MTX infusion her renal function had normalized. We report here our experience of a dramatic methotrexate level reduction caused by CPDG2 administration.

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Marc Ghannoum, Darren M. Roberts, David S. Goldfarb, Jesper Heldrup, Kurt Anseeuw, Tais F. Galvao, Thomas D. Nolin, Robert S. Hoffman, Valery Lavergne, Paul Meyers, Sophie Gosselin, Tudor Botnaru, Karine Mardini, David M. Wood
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Resumption of high‐dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients
Anthony M. Christensen, Jennifer L. Pauley, Alejandro R. Molinelli, John C. Panetta, Deborah A. Ward, Clinton F. Stewart, James M. Hoffman, Scott C. Howard, Ching‐Hon Pui, Alberto S. Pappo, Mary V. Relling, Kristine R. Crews
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Original Articles

Treatment Result of Pediatric Osteosarcoma with Intraarterial Cisplatin: Hyoung Soo Choi, Hyoung Jin Kang, Jun Ah Lee, Hyo Heong Han, Hyeon Jin Park, Eun Sun Yoo, Woo Sun Kim, Hee Young Shin, In One Kim, Sang Hoon Lee, Hyo Seop Ahn, Han Koo Lee; J Korean Cancer Assoc. 1998;30(1):169-177.

Abstract PDF: PURPOSE
This study was performed to determine the outcome after treatment of osteosarcoma with intraarterial cisplatin as a preoperative chematherapy regimen.
MATERIALS AND METHODS
Twenty five patients with extremity osteosarcoma were treated with intraarterial cisplatin at Seoul National University Children's Hospital from January 1987 to April 1996. The dose of cisplatin was 130 mg/m2 and three to six courses were repeated two- to three-week intervals, Systemic doxorubicin was added to six of these patients. This was followed by surgical resection(limb salvage or amputation) and postoperative adjuvant chemotherapy.
RESULTS
Limb-salvage was possible in twenty of these twenty five patients. Pulmonary metastasis was present in five patients at diagnosis and developed later in three patients. In six patients treated with systemic doxorubicin, pulmonary metastasis was absent at diagnosis and during follow-up period. Local recurrence after limb salvage was occurred in one patient and treated with amputation and systemic chemotherapy. Seven patients died from pulmonary metastssis and one from unknown cause. The follow-up duration of these patients was three to eighty eight months(median twenty two months) and the overall five-year survival and event free survival rate were 62.1% and 57.5%, respectively.
CONCLUSION
These data demonstrate that intraarterial cisplatin can be used as an effective regimen preoperatively for pediatric patients with extremity osteosarcoma. The combined use of systemic doxorubicin is expected to improve survival in patients with pulmonary metastasis.

3,140 View
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A monoclonal antibody to CD 35 molecule-a monoclonal antibody to follicular dendritic cell in lymphoid tissues-: Sung Hee Park, Hee Young Shin, Joon Kim; J Korean Cancer Assoc. 1993;25(5):744-750.

Abstract PDF: No abstract available.

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Experience of '8-drugs-in-a-day' chemotherapy for CNS primitive neuroectodermal tumor: Hee Young Shin, Hyo Sub Ahn; J Korean Cancer Assoc. 1993;25(5):707-716.

Abstract PDF: No abstract available.

1,963 View
12 Download

Study on the treatment of childhood acute lymphoblastic leukemia: Sang Oh Na, Hee Young Shin, Hyo Seop Ahn, Sang Kyu Park; J Korean Cancer Assoc. 1992;24(3):390-400.

Abstract PDF: No abstract available.

2,180 View
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Treatment of Childhood Acute Lymphoblastic Leukemia Diagnosed Jan . , 1978 Through Dec . , 1987 : Comparison between Standard - Risk and High - Risk Groups: Soon Ki Kim, Hee Young Shin, Hyo Seop Ahn; J Korean Cancer Assoc. 1990;22(3):539-549.

Abstract PDF: Of 328 children who were diagnosed as acute lymphoblastic leukemia at the Department of Pediatrics. Seoul National University Hospital from Jan., 1978 through Dec., 1987, 211 patients above one year af age were evaluable for induction chemotherapy. The leukemias were classified as standard risk (SR), comparison group (who had high-risk prognostic factors, but had been treated with standard regimen), or high- risk (HR) leukemia according to the prognostic criteria at diagnosis. Three regimens were compared and the results were as follows. 1) The complete remission (CR) rate was 97.1%(133/137), 81.0%(34/42) and 90.6%(29/32) in SR, comparison group. and HR group, respectively. And significant difference in the CR rate was seen between SR group and comparison group (p= 0.0001). 2) Of the patients remained in remission follow-up of each group showed 56.8% 5-yr disease-free survival (DFS)(+-5.9%, median follow-up 30 mo) in SR, 35.5% (+-9.1%, median 24 mo) in comparison group, and 76.0%(+- 8.5%, median 24 mo) in HR group. And significant difference in the 5yr-DFS rate were observed be(ween SR and comparison group (P = 0.007), between HR and comparison group (p = 0.002), respectively. 3) Induction failure was due to infection (n=2) bleeding (n=1) or uric acid nephropathy (n= 1) in SR drug resistance (n=3), infection (n=2), bleeding (n=2), or combind infection and bleeding (n=1) in comparison group, and bleeding (n=2) or infection (n= 1) in HR. Of the patients who were on maintenance chemotherapy in complete remission, 11 died due to infection: menigitis or meningoencephalitis (n=4), disseminated varicella (n=3), Pneumocystis carinii pneumonia (n=2), and sepsis (n=2). 4) In SR group, 29 patients experienced relapse: BM(n=18), CNS(n=3), BM and CNS(n=4), and testes (n=4). Two- third (n = 19) of them relapsed between 6mo to 2yr after initial remission. In comparison graup, 20 relapsed: BM (n= 10), CNS(n=2), BM and CNS (n=3), testes (n=4), and testes and CNS(n =1), Mostly they relapsed within the first 2 years after remission. In HR group, all patients (BM 3 and CNS 1) experienced relapse from 1 yr to 1 1/2 yr after initial remission.

2,217 View
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Effect of Filgrastim ( rhG - CSF ) on Chemotherapy Induced Neutropenia in Pediatric Acute Myelogenous Leukemia Patients: Hee Young Shin, Hee Young Shin, Seong Hoon Hah, Hong Hoe Koo, Hyo Seop Ahn; J Korean Cancer Assoc. 1994;26(1):136-144.

Abstract PDF: To determine the safety and efficacy of rhG-CSF on chemotherapy induced neutropenia in pediatric AML patients, we conducted a prospective controlled study in 17 patiens with AML at Seoul National University Childrens Hospital from July, 1993 to January, 1994. High dose cytosine arabinoside(Ara-C, 3gm/m for four times every 12 hours) with L-asparaginase 6,000 u/m) were given to 13 patients as Group I control and after the recovery of WBC, same chemo- therapy followed by G-CSF(50 ug/m for 10 days) were given as Group I study. In Group II study, high dose Ara-C(3gm/m(2) for 8 times every 12 hours) were given to 11 patients with AML followed by G-CSF(150 ug/m for 10 days). Recovery of the absolute neutrophil counts to more than 1,000/mm' was significantly faster in the G-CSF group than in the control group(P< 0.01) and the absolute neutrophil counts on day 14 of chemotherapy was significantly higher in G-CSF group(P<0.01). The toxicity of G-CSF was minimal and there was no evidence of accel- erated growth of leukemic blasts during the G-CSF treatment. In conclusion, Filgrastim(rhG- CSF) promotes the recovery of neutrophils and shortens the duration of neutropenia induced by the chemotherapy in pediatric acute myelogenous leukemia.

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Effects of cancer nervous System Irradiation on Neuropsychologic Functioning in Long - term Survivors of Childhood Acute Lymphoblastic Leukemia: Ji Eun Choi, Hee Young Shin, In One Kim, Kyung Mo Yeon, In Young Chae, Soo Churl Cho, Yong Seung Hwang, Hyo Seop Ahn; J Korean Cancer Assoc. 1995;27(2):303-316.

Abstract PDF: Long-term adverse neuropsychologic sequelae are frequently observed in pediatric patients treated for acute lymphoblastic leukemia(ALL). In this study, 10 children in continuous com- plete remission from ALL were given tests of IQ, neuropsychologic assessment, waking EEG, brain MRI to assess neuropsychologic functioning minimum 2 years after CNS prophylaxis. All children were free of CNS disease at diagnosis and had received CNS prophylactic treatment with 1,800 cGy cranial irradiation plus intrathecal methotrexate. Male patients had a significant decline in coding compared with female patients(P<0.01) and those evaluated beyond age of 10-year-old had a greater decline in performance IQ compared with those evaluated under age of 10-year-old(P<0.01). One of the 10 children(10%) showed white matter changes on MRI attributable to therapy. All children had no significant lower mean IQ, but lower achievement with regard to arithmetic skills, picture arrangement than other tests. We conclude that prophylactic CNS therapy may cause cognitive dysfunctions and the white matter changes but its value and significance during follow-up should be assessed in well designed longitudinal research studies.

2,738 View
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