Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.
Leuk Lymphoma. 2020 Aug;61(8):1920-1931. doi: 10.1080/10428194.2020.1749604. Epub 2020 Apr 7.
Pharmacokinetic (PK) conflicts can arise between supportive care medications (SCM) and chemotherapy in children with hematologic malignancy (HM). In this retrospective study, medical records for children (28 days-18 years) diagnosed with HM and receiving an SCM antimicrobial were collected from a hospital network between 1 May 2000 and 31 December 2014. PK drug-gene associations were obtained from a curated pharmacogenomics database. Among 730 patients (median age of 7.5 (IQR 3.7-13.9) years), primarily diagnosed with lymphoid leukemia (52%), lymphoma (28%), or acute myeloid leukemia (16%), chemotherapy was administered in 2846 hospitalizations. SCM accounted for 90.5% ( = 448) of distinct drugs with 93% ( = 679) of children, receiving ≥5 different SCM/hospitalization. Same-day SCM/chemotherapeutic PK gene overlap occurred in 48.3% of hospitalizations and was associated with age ( = 0.026), number of SCM, HM subtype, surgery, and hematopoietic stem cell transplant ( < 0.0001). A high and variable SCM burden among children with HM receiving chemotherapy poses a risk for unanticipated PK conflicts.
在患有血液恶性肿瘤 (HM) 的儿童中,支持性护理药物 (SCM) 和化疗之间可能会出现药代动力学 (PK) 冲突。在这项回顾性研究中,从 2000 年 5 月 1 日至 2014 年 12 月 31 日,从一个医院网络中收集了诊断患有 HM 并接受 SCM 抗菌药物治疗的儿童(28 天至 18 岁)的病历。PK 药物-基因关联从经过精心策划的药物基因组学数据库中获得。在 730 名患者中(中位数年龄为 7.5(IQR 3.7-13.9)岁),主要诊断为淋巴白血病(52%)、淋巴瘤(28%)或急性髓细胞性白血病(16%),在 2846 次住院治疗中使用了化疗。SCM 占 448 种不同药物中的 90.5%(=448),93%(=679)的儿童每次住院接受≥5 种不同的 SCM。48.3%的住院治疗中发生了同一天的 SCM/化疗 PK 基因重叠,与年龄(=0.026)、SCM 数量、HM 亚型、手术和造血干细胞移植有关(<0.0001)。接受化疗的 HM 儿童的 SCM 负担高且变化较大,存在不可预测的 PK 冲突风险。