Weil Elizabeth, Zook Felicia, Oxencis Carolyn, Canadeo Angela, Urmanski Angela, Waggoner Mindy, Eastwood Daniel, Pasquini Marcelo, Hamadani Mehdi, Hari Parameswaran
Hematology/Oncology, Froedtert & the Medical College of Wisconsin, Milwaukee, Wisconsin.
Investigational Drug Services, Froedtert & the Medical College of Wisconsin, Milwaukee, Wisconsin.
Biol Blood Marrow Transplant. 2017 Jun;23(6):952-957. doi: 10.1016/j.bbmt.2017.02.020. Epub 2017 Mar 10.
Owing to interpatient variability in busulfan exposure, therapeutic monitoring of busulfan is often used in myeloablative allogeneic transplantation to ensure that patients are near the optimal steady-state goal of 900 ng/mL. One challenge in therapeutic monitoring of busulfan is the brief course of busulfan treatment, requiring prompt analysis and dose adjustments as needed. Pharmacokinetic evaluation of a busulfan test dose before the start of the conditioning regimen would allow for all conditioning regimen doses to be given at the calculated optimized dose. An observational study was completed to evaluate the effects of a busulfan test dose of 0.9 mg/kg administered before the start of a myeloablative intravenous busulfan-based conditioning regimen. Sixty adult patients who received a busulfan conditioning regimen were reviewed, including 30 patients prior to the implementation of the busulfan test dose (pretest dose group) and 30 patients who received the busulfan test dose (posttest dose group). The primary objective was a pharmacokinetic evaluation of the percentage of patients who achieved the desired steady-state goal using the test dose strategy. The safety and efficacy of the busulfan test dose were evaluated as well. The average busulfan steady-state level after the first dose of the conditioning regimen was significantly lower in the pre-test dose group compared with the post-test dose group (660 ng/mL versus 879.9 ng/mL; P < 0.001). Compared with the post-test dose group, significantly fewer patients in the pre-test dose group were within 10% of the busulfan steady-state goal (10% versus 73.3%; P < 0.001) or within 5% of the goal (0% versus 53%; P < 0.001). Requirements for parenteral nutrition and/or patient-controlled analgesia owing to mucositis and rates of veno-occlusive disease were not significantly different between the pre-test dose group and the post-test dose group. The rates of disease relapse, mortality, and acute graft-versus-host disease were similar in the two groups. A pretransplantation busulfan test dose of 0.9 mg/kg improved the patients' ability to reach therapeutic busulfan target levels after the first conditioning dose and resulted in fewer adjustments during conditioning. The use of a busulfan test dose did not significantly increase patients' risk of mucositis or other safety outcomes.
由于患者间白消安暴露存在差异，在清髓性异基因移植中常采用白消安治疗监测，以确保患者接近900 ng/mL的最佳稳态目标。白消安治疗监测中的一个挑战是白消安治疗疗程短暂，需要根据需要迅速进行分析和剂量调整。在预处理方案开始前对白消安试验剂量进行药代动力学评估，将使所有预处理方案剂量都能按照计算出的优化剂量给予。完成了一项观察性研究，以评估在基于白消安静脉输注的清髓性预处理方案开始前给予0.9 mg/kg白消安试验剂量的效果。回顾了60例接受白消安预处理方案的成年患者，包括在实施白消安试验剂量前的30例患者（试验剂量前组）和接受白消安试验剂量的30例患者（试验剂量后组）。主要目的是使用试验剂量策略对达到期望稳态目标的患者百分比进行药代动力学评估。还评估了白消安试验剂量的安全性和有效性。与试验剂量后组相比，试验剂量前组在预处理方案首剂后的白消安平均稳态水平显著更低（660 ng/mL对879.9 ng/mL；P < 0.001）。与试验剂量后组相比，试验剂量前组中白消安稳态目标值在±10%以内的患者显著更少（10%对73.3%；P < 0.001）或在±5%以内的患者显著更少（0%对53%；P < 0.001）。试验剂量前组和试验剂量后组在因黏膜炎导致的肠外营养和/或患者自控镇痛需求以及静脉闭塞性疾病发生率方面无显著差异。两组的疾病复发率、死亡率和急性移植物抗宿主病发生率相似。移植前给予0.9 mg/kg白消安试验剂量可提高患者在首次预处理剂量后达到白消安治疗目标水平的能力，并减少预处理期间的剂量调整。使用白消安试验剂量并未显著增加患者发生黏膜炎或其他安全结局的风险。
