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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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.

Citations

Citations to this article as recorded by

Exploring the effects of topoisomerase II inhibitor XK469 on anthracycline cardiotoxicity and DNA damage
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
Pediatric Cardio-Oncology: Screening, Risk Stratification, and Prevention of Cardiotoxicity Associated with Anthracyclines
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
Current Problems in Cardiology.2022; 47(10): 100932. CrossRef
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
Cancer.2022; 128(4): 788. CrossRef
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
The Lancet Child & Adolescent Health.2022; 6(12): 885. CrossRef
Cardiotoxicity After Anthracycline Chemotherapy for Childhood Cancer in a Multiethnic Asian Population
Varen Zhi Zheng Tan, Nicole Min Chan, Wai Lin Ang, Soe Nwe Mya, Mei Yoke Chan, Ching Kit Chen
Frontiers in Pediatrics.2021;[Epub] CrossRef
Early-onset Cardiotoxicity assessment related to anthracycline in children with leukemia. A Prospective Study
Adriana Linares Ballesteros, Roy Sanguino Lobo, Juan Camilo Villada Valencia, Oscar Arévalo Leal, Diana Constanza Plazas Hernández, Nelson Aponte Barrios, Iván Perdomo Ramírez
Colombia Medica.2021; 52(1): e2034542. CrossRef
Mechanisms and Insights for the Development of Heart Failure Associated with Cancer Therapy
Claire Fraley, Sarah A. Milgrom, Lavanya Kondapalli, Matthew R. G. Taylor, Luisa Mestroni, Shelley D. Miyamoto
Children.2021; 8(9): 829. CrossRef
Dantrolene Attenuates Cardiotoxicity of Doxorubicin Without Reducing its Antitumor Efficacy in a Breast Cancer Model
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
Investigation of Structure-Activity Relationships of Dexrazoxane Analogs Reveals Topoisomerase IIβInteraction as a Prerequisite for Effective Protection against Anthracycline Cardiotoxicity
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

Reactions Weekly.2019; 1741(1): 28. CrossRef
Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series
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
Cardio-Oncology.2019;[Epub] CrossRef
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
Cardio-Oncology.2019;[Epub] CrossRef
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
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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

Abstract PDF PubReader ePub

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.

Citations

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