A Study to Evaluate the Effectiveness and Safety of Prephase Steroid Treatment before Remission Induction Chemotherapy in Patients with Pediatric Acute Lymphoblastic Leukemia Using Common Data Model-Based Real-World Data: A Retrospective Observational Study

Yoona Choi; Bo Kyung Kim; Jung-Hyun Won; Jae Won Yoo; Wona Choi; Surin Jung; Jae Yoon Kim; In Young Choi; Nack-Gyun Chung; Jae Wook Lee; Jung Yoon Choi; Hyoung Jin Kang; Howard Lee

doi:10.2147/CLEP.S454263

A Study to Evaluate the Effectiveness and Safety of Prephase Steroid Treatment before Remission Induction Chemotherapy in Patients with Pediatric Acute Lymphoblastic Leukemia Using Common Data Model-Based Real-World Data: A Retrospective Observational Study

Clin Epidemiol. 2024 Apr 22:16:293-304. doi: 10.2147/CLEP.S454263. eCollection 2024.

Authors

Yoona Choi^#^{1

2}, Bo Kyung Kim^#^{3

4}, Jung-Hyun Won^{2

5}, Jae Won Yoo⁶, Wona Choi⁷, Surin Jung⁷, Jae Yoon Kim^{7

8}, In Young Choi⁷, Nack-Gyun Chung⁶, Jae Wook Lee⁶, Jung Yoon Choi^{3

4}, Hyoung Jin Kang^{3

4

9}, Howard Lee^{1

2

5

10

11}

Affiliations

¹ Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
² Center for Convergence Approaches in Drug Development, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
³ Department of Pediatrics, Seoul National University Hospital, Seoul, Republic of Korea.
⁴ Seoul National University Cancer Research Institute, Seoul, Republic of Korea.
⁵ Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
⁶ Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea.
⁷ Department of Medical Informatics, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea.
⁸ Department of Biomedicine & Health Sciences, the Catholic University of Korea, Seoul, Republic of Korea.
⁹ Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.
¹⁰ Advanced Institutes of Convergence Technology, Suwon, Republic of Korea.
¹¹ Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Republic of Korea.

^# Contributed equally.

Abstract

Background: Rapid reduction of leukemic cells in the bone marrow during remission induction chemotherapy (RIC) can lead to significant complications such as tumor lysis syndrome (TLS). We investigated whether prephase steroid treatment before RIC could decrease TLS incidence and improve overall survival in pediatric patients with acute lymphoblastic leukemia (ALL).

Methods: Data were extracted from the Common Data Model databases in two tertiary-care hospitals in Seoul, South Korea. Patients were classified into the treated or untreated group if they had received RIC with prephase steroid treatment ≥7 days before RIC in 2012-2021 or not, respectively. Stabilized Inverse Probability of Treatment Weighting (sIPTW) was applied to ensure compatibility between the treated and untreated groups. The incidence of TLS within 14 days of starting RIC, overall survival (OS), and the incidence of adverse events of special interest were the primary endpoints. Multiple sensitivity analyses were performed.

Results: Baseline characteristics were effectively balanced between the treated (n=308.4) and untreated (n=246.6) groups after sIPTW. Prephase steroid treatment was associated with a significant 88% reduction in the risk of TLS (OR 0.12, 95% CI: 0.03-0.41). OS was numerically greater in the treated group than in the untreated group although the difference was not statistically significant (HR 0.64, 95% CI 0.25-1.64). The treated group experienced significantly elevated risks for hyperbilirubinemia and hyperglycemia. The reduction in TLS risk by prephase steroid treatment was maintained in all of the sensitivity analyses.

Conclusion: Prephase steroid treatment for ≥7 days before RIC in pediatric patients with ALL reduces the risk of TLS, while careful monitoring for toxicities is necessary. If adequately analyzed, real-world data can provide crucial effectiveness and safety information for proper management of pediatric patients with ALL, for whom prospective randomized studies may be difficult to perform for ethical and practical reasons.

Keywords: common data model; pediatric acute lymphoblastic leukemia; prephase steroid treatment; remission induction chemotherapy; tumor lysis syndrome.

Grants and funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI22C0464). Additionally, this research is partly supported by the BK21FOUR Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education (5120200513755).