LAUSR

Background Pneumocystis jirovecii (PJP) infections are a significant cause of morbidity and mortality in recipients of hematopoietic cell transplantations (HCT), and PJP prophylaxis is a standard of care. The gold standard for PJP prophylaxis is sulfamethoxazole and trimethoprim (SMX/TMP), however, SMX/TMP is known to cause neutropenia so it is often avoided in the pre- and early post-HCT period. Alternatively, pentamidine can be administered in the early post HCT period without concern of marrow suppression. Pentamidine is a substrate of the CYP2C19, a CYP450 enzyme with known polymorphisms affecting metabolizer activity. A previous adult study demonstrated that patients with at least one ‘no function' allele were at an increased risk of serious adverse effects including death. We sought to determine the influence of CYP2C19 metabolizer status on the safety and efficacy of pentamidine in pediatric HCT population. Methods A retrospective chart review was conducted on all patients undergoing HCT at Cincinnati Children's Hospital between June 2013 and September 2018. Analysis of single nucleotide polymorphisms of CYP2C19 (*2, *3, *4, *5, *6, *7, *8, *17) were performed on a Taqman™ Low Density Array as part of routine clinical care. Incidence of breakthrough PJP infections, pentamidine discontinuation due to adverse effects as well as patient and transplant demographic information were collected. Results A total of 319 patients received pentamidine and had CYP2C19 genotyping perfomed during the study period.There were 8 poor metabolizers (two no function alleles), 101 intermediate metabolizers (one no function allele and one normal or increased function allele), 128 normal metabolizers (two normal function alleles) and 82 ultrarapid metabolizers (two increased function alleles or one normal allele and one increased function allele). There was no difference in the number of patients who discontinued therapy due to adverse events among metabolizer status groups, nor was there a difference in the number of breakthrough PJP infections (Table 1). Conclusions Our study demonstrates that, in contrast to the adult study, it is safe and efficacious to administer pentamidine in pediatric HCT patients regardless of CYP2C19 metabolizer status.