ABSTRACT Background Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) can potentially cure various hematologic disorders. However, transplant‐related complications, including hemorrhagic cystitis (HC), remain major causes of adverse outcomes and decreased survival. This study examines the associations of HC with pharmacogenetic single nucleotide polymorphisms (SNPs) and clinical characteristics. Methods This retrospective study included 259 pediatric patients who underwent allo‐HSCT. HC was predefined as the primary endpoint, and other major complications were analyzed as secondary exploratory outcomes. Bone marrow samples were collected at initial diagnosis for genomic DNA extraction. SNP genotyping was performed by targeted next‐generation sequencing via a customized 30‐gene panel. Results Among the 30 SNPs analyzed, all except CYP2C19 (c.99T > C) were in Hardy‐Weinberg equilibrium (all p > 0.05). In univariate Cox regression, CYP2C19 (c.681G > A) GA/AA genotype, older age, higher body weight, haploidentical transplantation, use of cord blood in the graft, peri‐engraftment syndrome (peri‐ES), severe acute graft‐versus‐host disease, and cytomegalovirus infection were significantly associated with an increased risk of HC, whereas HLA 9/10‐10/10 match appeared protective (all p A) GA/AA (hazard ratio (HR) = 1.90, p = 0.021), older age ( HR = 2.14, p = 0.036), and peri‐ES ( HR = 1.86, p = 0.034) as independent risk factors for HC. Conclusion This study demonstrates that CYP2C19 (c.681G > A) GA/AA genotype, older age, and peri‐ES are each independent risk factors for HC after allo‐HSCT. These findings highlight the value of pharmacogenetic and clinical profiling in predicting susceptibility to HC and guiding personalized preventive strategies, contributing to a deeper understanding of the interplay among genetic predisposition, immune responses, and chemotherapy‐related toxicity in HC pathogenesis.
Zhang et al. (2026) studied this question.