Gurevich Ekaterina, Hayoz Michael, Aebi Yolanda, Largiadèr Carlo R, Mansouri Taleghani Behrouz, Bacher Ulrike, Pabst Thomas
Department of Medical Oncology, Inselspital, University of Bern, CH-3010 Bern, Switzerland.
Department of Clinical Chemistry, Inselspital, University of Bern, CH-3010 Bern, Switzerland.
Cancers (Basel). 2022 Feb 17;14(4):1024. doi: 10.3390/cancers14041024.
(1) Background: High-dose chemotherapy (HDCT) before autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML) patients predominantly combines busulfan with cyclophosphamide or melphalan. Treosulfan compares favorably regarding lower inter-individual bioavailability and neurotoxicity, but so far, had not been studied before ASCT in AML. (2) Methods: This single-center study investigated AML patients undergoing ASCT in CR1 between November 2017 and September 2020. The first 16 patients received busulfan 16 mg/kg b.w. (days -5 to -2) and melphalan 140 mg/m (day -1) (BuMel). In a subsequent (TreoMel) cohort, 20 patients received treosulfan 14 g/m (days -4 to -2) and melphalan. Plasma concentrations of busulfan and treosulfan were determined by mass spectrometry. (3) Results: Neutrophil engraftment and platelet recovery were similar, and PFS and OS were comparable. In only the BuMel cohort, patients reported central nervous toxicities, including seizures (6%) and encephalopathy (12%). The mean AUC for busulfan was 1471.32 μMmin, and for treosulfan it was 836.79 mg/Lh, with ranges of 804.1-2082 μMmin and 454.2-1402 mg/Lh. The peak values for busulfan ranged between 880.19-1734 μg/L and for treosulfan between 194.3-489.25 mg/L. (4) Conclusions: TreoMel appears to be safe and effective for pre-ASCT treatment in AML patients. Due to considerable interindividual biovariability, pharmacologic monitoring may also be warranted for the use of treosulfan.
(1) 背景：急性髓系白血病（AML）患者在自体干细胞移植（ASCT）前进行的大剂量化疗（HDCT）主要是将白消安与环磷酰胺或美法仑联合使用。曲奥舒凡在个体间生物利用度和神经毒性较低方面具有优势，但迄今为止，尚未在AML患者的ASCT前进行过研究。(2) 方法：这项单中心研究调查了2017年11月至2020年9月期间处于完全缓解期（CR1）接受ASCT的AML患者。前16名患者接受白消安16mg/kg体重（第-5天至-2天）和美法仑140mg/m²（第-1天）（白消安-美法仑方案）。在随后的（曲奥舒凡-美法仑方案）队列中，20名患者接受曲奥舒凡14g/m²（第-4天至-2天）和美法仑。通过质谱法测定白消安和曲奥舒凡的血浆浓度。(3) 结果：中性粒细胞植入和血小板恢复情况相似，无进展生存期（PFS）和总生存期（OS）相当。仅在白消安-美法仑方案队列中，患者报告了中枢神经毒性，包括癫痫发作（6%）和脑病（12%）。白消安的平均曲线下面积（AUC）为1471.32μM·min，曲奥舒凡的为836.79mg/L·h，范围分别为804.1 - 2082μM·min和454.2 - 1402mg/L·h。白消安的峰值在880.19 - 1734μg/L之间，曲奥舒凡的在194.3 - 489.25mg/L之间。(4) 结论：曲奥舒凡-美法仑方案在AML患者ASCT前治疗中似乎是安全有效的。由于个体间生物变异性较大,使用曲奥舒凡时也可能需要进行药物监测。
