评估围手术期儿童癌症患者异基因造血干细胞移植后环孢素A剂量的最优化方法。
Optimizing cyclosporine A dose post allogeneic hematopoietic stem cell transplantation in paediatric cancer patients.
发表日期:2023 Aug 01
作者:
Mennatallah Elnaggar, Hanafy Hafez, Amr Abdallah, Mahmoud Hamza, Marwa M Khalaf, Alaa El-Haddad
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
环孢霉素A(CSA)的剂量因药代动力学方面的患者内部和患者间的重大变异而变得复杂,这些变异受不同因素的影响。我们的目的是评估可能影响CSA剂量及其血浆水平的各种因素。本回顾性研究纳入了在埃及57357儿童肿瘤医院接受同种异体造血干细胞移植的小儿癌症患者,采用CSA作为移植物抗宿主病预防药物。CSA初始剂量为1.5毫克/千克静脉注射,每12小时一次。然后,根据药物浓度和毒副作用进行调节。使用Emit 2000环孢霉素特异性测定来评估每周2-3次的环孢霉素A血药浓度峰值。此外,还分析了可能影响环孢霉素A水平的因素,如年龄、性别、体重和抗真菌药物的使用,以确定它们对CSA血浆水平的影响。
本研究纳入了119名患者。中位年龄为10岁;其中43%的患者使用伏立康唑作为预防性抗真菌药物。多元分析显示,女性患者、年龄>9岁或使用伏立康唑的患者需要较低的初始CSA剂量才能达到目标水平。在年龄>9岁、并使用伏立康唑的患者中,使用1.5毫克/千克静脉注射每12小时一次的剂量可达到所期望的血浆浓度水平的概率较高(93%)。而对于年龄≤9岁且不使用伏立康唑的患者,需要>1.5毫克/千克静脉注射每12小时一次的剂量,以达到预期水平的概率为89%。
该研究表明,初始CSA剂量应考虑患者的年龄和抗真菌药物的使用。年龄>9岁和/或使用伏立康唑的患者可能需要较低的初始CSA剂量,并可从1.5毫克/千克静脉注射每12小时一次开始。
Cyclosporine A (CSA) dosing has been complicated by considerable intra-patient and inter-patient variability in pharmacokinetics, which is affected by different factors. We aimed to assess the various factors that might affect the CSA dose and its plasma level.This retrospective study included paediatric cancer patients who underwent allogeneic hematopoietic stem cell transplant at the Children's Cancer Hospital Egypt 57357 from matched related donors with CSA as graft versus host disease prophylaxis. The CSA initial dose was 1.5 mg/kg IV Q12H. Then, it was titrated according to the level and drug toxicity. Cyclosporine A trough levels were assessed two to three times per week using the Emit 2000 cyclosporine-specific assay. Moreover, factors that may affect cyclosporine levels, such as age, sex, weight and the antifungal used, were analyzed to determine their effect on CSA plasma levels.There were 119 patients included in the study. The median age was 10 years; and 43% of them used voriconazole as a prophylactic antifungal. The multivariate analysis revealed that female patients, those >9 years or on voriconazole reached the target level at low initial CSA doses. A higher probability (93%) of reaching the desired plasma level with doses 1.5 mg/kg IV Q12H was observed among patients >9 years, and on voriconazole. While those who were ≤9 years and not on voriconazole required doses >1.5 mg/kg IV Q12H, with an 89% probability of reaching the desired level.This study suggests that the initial CSA dose should consider the patient's age and the antifungal used. Patients >9 years and/or on voriconazole may require lower initial CSA doses and could start with 1.5 mg/kg IV Q12H.