Abstract：
BACKGROUND: The aims of this study are to report our experience with treosulfan-based conditioning regimens for patients with non-malignant hematologic conditions, correlating clinical outcomes at different time points post-transplant with treosulfan exposure (AUC).
METHODS: This study was a single-center observational study investigating overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) end-points post-transplant. The consequences of treosulfan AUC with respect to toxicity, correction of underlying disease, and long-term chimerism were also explored using pharmacokinetic analysis.
RESULTS: Forty-six patients received 49 transplants with treosulfan and fludarabine-based conditioning between 2005 and 2023. Twenty-four patients also received thiotepa. Donor chimerism was assessed on either whole blood or sorted cell lines at different time points post-transplant. Thirty-nine patients received treosulfan pharmacokinetic assessment to evaluate cumulative AUC, with five infants receiving real-time assessment to facilitate daily dose adjustment. OS, DFS, and EFS were 87%, 81%, and 69%, respectively. Median follow-up was 32.1 months (range 0.82-160 months) following transplant. Lower EFS was associated with patient age (<1 year; p = .057) and lower cumulative treosulfan dose (<42 g/m2; p = .003). Stable donor chimerism in B-cell, NK-cell, and granulocyte lineages at 1-year post-transplant were more prevalent in patients receiving thiotepa conditioning. Two infants required daily dose adjustment to treosulfan to avoid high AUC.
CONCLUSIONS: Excellent clinical outcomes and stable chimerism were observed in this patient series. The addition of thiotepa conferred no significant toxicity and trended toward sustained ongoing donor engraftment. Correlating treosulfan AUC with long-term patient outcomes is required.
METHODS: This study was a single-center observational study investigating overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) end-points post-transplant. The consequences of treosulfan AUC with respect to toxicity, correction of underlying disease, and long-term chimerism were also explored using pharmacokinetic analysis.
RESULTS: Forty-six patients received 49 transplants with treosulfan and fludarabine-based conditioning between 2005 and 2023. Twenty-four patients also received thiotepa. Donor chimerism was assessed on either whole blood or sorted cell lines at different time points post-transplant. Thirty-nine patients received treosulfan pharmacokinetic assessment to evaluate cumulative AUC, with five infants receiving real-time assessment to facilitate daily dose adjustment. OS, DFS, and EFS were 87%, 81%, and 69%, respectively. Median follow-up was 32.1 months (range 0.82-160 months) following transplant. Lower EFS was associated with patient age (<1 year; p = .057) and lower cumulative treosulfan dose (<42 g/m2; p = .003). Stable donor chimerism in B-cell, NK-cell, and granulocyte lineages at 1-year post-transplant were more prevalent in patients receiving thiotepa conditioning. Two infants required daily dose adjustment to treosulfan to avoid high AUC.
CONCLUSIONS: Excellent clinical outcomes and stable chimerism were observed in this patient series. The addition of thiotepa conferred no significant toxicity and trended toward sustained ongoing donor engraftment. Correlating treosulfan AUC with long-term patient outcomes is required.
摘要：
背景：本研究的目的是报告我们对非恶性血液学疾病患者使用以曲硫丹为基础的调理方案的经验，将移植后不同时间点的临床结果与曲硫丹暴露（AUC）相关联。
方法：本研究是一项单中心观察性研究，调查总生存期（OS），无病生存率（DFS），移植后无事件生存（EFS）终点。曲硫丹AUC对毒性的影响，矫正潜在疾病，还使用药代动力学分析探索了长期嵌合状态。
结果：在2005年至2023年期间，46名患者接受了49例移植，其中包括基于曲硫丹和氟达拉滨的预处理。24名患者也接受了thiotepa。在移植后的不同时间点对全血或分选的细胞系评估供体嵌合体。39例患者接受了曲硫丹药代动力学评估，以评估累积AUC，五名婴儿接受实时评估，以促进每日剂量调整。操作系统,DFS,EFS为87%，81%,69%,分别。移植后的中位随访时间为32.1个月（范围0.82-160个月）。较低的EFS与患者年龄（<1岁；p=0.057）和较低的累积曲硫丹剂量（<42g/m2；p=0.003）相关。B细胞中稳定的供体嵌合状态，NK细胞，在接受Thiotepa预处理的患者中，移植后1年的粒细胞谱系更为普遍。两名婴儿需要调整每日剂量以曲硫丹，以避免高AUC。
结论：在该患者系列中观察到优异的临床结果和稳定的嵌合状态。添加thiotepa不会产生明显的毒性，并且倾向于持续进行的供体植入。需要将曲硫丹的AUC与长期患者结果相关联。
方法：本研究是一项单中心观察性研究，调查总生存期（OS），无病生存率（DFS），移植后无事件生存（EFS）终点。曲硫丹AUC对毒性的影响，矫正潜在疾病，还使用药代动力学分析探索了长期嵌合状态。
结果：在2005年至2023年期间，46名患者接受了49例移植，其中包括基于曲硫丹和氟达拉滨的预处理。24名患者也接受了thiotepa。在移植后的不同时间点对全血或分选的细胞系评估供体嵌合体。39例患者接受了曲硫丹药代动力学评估，以评估累积AUC，五名婴儿接受实时评估，以促进每日剂量调整。操作系统,DFS,EFS为87%，81%,69%,分别。移植后的中位随访时间为32.1个月（范围0.82-160个月）。较低的EFS与患者年龄（<1岁；p=0.057）和较低的累积曲硫丹剂量（<42g/m2；p=0.003）相关。B细胞中稳定的供体嵌合状态，NK细胞，在接受Thiotepa预处理的患者中，移植后1年的粒细胞谱系更为普遍。两名婴儿需要调整每日剂量以曲硫丹，以避免高AUC。
结论：在该患者系列中观察到优异的临床结果和稳定的嵌合状态。添加thiotepa不会产生明显的毒性，并且倾向于持续进行的供体植入。需要将曲硫丹的AUC与长期患者结果相关联。
