Dental developmental complications in pediatric hematopoietic stem cell transplantation patients: A study using CMC clinical data warehouse

PLOS ONE RESEARCH ARTICLE Dental developmental complications in pediatric hematopoietic stem cell transplantation patients: A study using CMC clinical data warehouse Jaehyun Kim1, Hee Jin Lim1, Ja Hyeong Ku1, Yoon-Ah Kook1, Nack-Gyun Chung2, Yoonji Kim ID1* a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Orthodontics, Seoul Saint Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, 2 Department of Pediatrics, Seoul Saint Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea * , Abstract OPEN ACCESS Citation: Kim J, Lim HJ, Ku JH, Kook Y-A, Chung N-G, Kim Y (2022) Dental developmental complications in pediatric hematopoietic stem cell transplantation patients: A study using CMC clinical data warehouse. PLoS ONE 17(12): e0279579. https://doi.org/10.1371/journal.pone.0279579 Objective This study aimed to investigate the prevalence and extent of dental developmental complications in patients who have undergone pediatric hematopoietic stem cell transplantation (SCT) and identify the risk factors. Editor: Nazmul Haque, TotiCell Limited, Bangladesh, BANGLADESH Received: March 10, 2022 Accepted: December 10, 2022 Published: December 22, 2022 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0279579 Copyright: © 2022 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All data are available from a public repository (Kim J, Lim HJ, Ku JH, Kook YA, Chung NG, Kim Y. Dental developmental complications in pediatric hematopoietic stem cell Materials and methods We retrospectively investigated the clinical data warehouse of the Catholic Medical Center information system for identifying patients who: 1) visited the Department of Pediatrics between 2009 and 2019, 2) underwent SCT under the age of 10, and 3) had panoramic radiographs. Thus 153 patients were included in this study. The prevalence and extent of tooth agenesis, microdontia, and root malformation were assessed using panoramic radiographs obtained after SCT, and the risk factors were analyzed using regression analysis. Results All 153 patients had at least one dental anomaly. When grouped according to the age at initial chemotherapy (� 2.5; 2.6–5.0; 5.1–7.5; > 7.5 years), the prevalence of agenesis showed statistically significant differences among the different age groups (P < 0.001). The prevalence of agenesis was highest in the youngest age group. As the initial age at chemotherapy increased, the number of affected teeth per patient decreased for all three anomalies. The location of the affected tooth was also influenced by the age at initial chemotherapy. Regression analysis demonstrated that young age at initial chemotherapy was a risk-increasing factor for tooth agenesis and microdontia. PLOS ONE | https://doi.org/10.1371/journal.pone.0279579 December 22, 2022 1 / 13 PLOS ONE transplantation patients: A study using CMC clinical data warehouse. 2022. Figshare Digital Repository. https://doi.org/10.6084/m9.figshare.21397647). Funding: This study was supported by Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea (ZC20RISI0730 / https://www. cmcseoul.or.kr/en.common.main.main.sp) and National Research Found government (MSIT) (No. 2021R1F1A1049557 / https://www.nrf.re.kr/eng/ main/). YK received all award above. All of these funding sources had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, preparation of the manuscript, or decision to submit results. There was no additional external funding received for this study. Competing interests: The authors have declared that no competing interests exist. Dental developmental complications in pediatric hematopoietic stem cell transplantation patients Conclusions The age at initial chemotherapy may be a critical factor in determining the type, extent, and location of dental complications after SCT. These results suggest that careful dental followup and timely treatment are recommended for pediatric patients undergoing SCT. Introduction As the survival rate of childhood cancer patients increases, improving the quality of life (QOL) has become an essential task for cancer therapy [1, 2]. Few survivors are free of long-term side effects, and follow-up for these patients is essential for maintaining their QOL. Hematopoietic stem cell transplantation (SCT) plays a critical role in the treatment of malignancies in pediatric patients. Disturbances in dental development have been known to occur after SCT combined with chemotherapy and/or total body irradiation (TBI) in patients with childhood cancer [3–6]. Dental complications are not life-threatening; however, they may have a profound impact on QOL. Developmental dental anomalies include tooth agenesis, microdontia (small-sized tooth), impaired and arrested root development, such as short V-shaped roots, and enamel hypoplasia [7–10]. These anomalies are characterized by defective hard tissue formation. Näsman et al. reported that all developing teeth were affected by multi-agent chemotherapy and radiation therapy [11] and that dental sequelae are irreversible. In addition, impaired salivary function [12], increased risk of dental caries, disturbances in craniofacial growth, and higher risk of developing secondary oral tumors have also been reported [3]. The prevalence of dental anomalies among pediatric patients with cancer is relatively high at 55.5%, compared with the prevalence of 6.7% among healthy individuals [13, 14]. Other studies have reported that the prevalence of dental anomalies ranged from 50–100% in patients who underwent SCT [15] and that disturbances in root development were present in all patients who underwent SCT [7]. A large amount of long-term data is required to evaluate late dental complications after SCT [16]. Most studies analyzed only specific factors in a limited numbers of samples [7, 17– 19]. In addition, there are conflicting reports suggesting that dental disturbances can be attributed to chemotherapy regimens [20], the age of the patient and the use of cranial radiation therapy [11], or the effect of TBI [18]. From our clinical experience of treating a large number of adult and pediatric patients who underwent SCT, we postulated that developmental dental complications may only occur in growing individuals who have developing teeth, and the types and extent of dental complications after SCT may depend on the timing of a (...truncated)