University Cancer Center Hamburg, Department of Stem Cell Transplantation, Martinistr. 52, 20246 Hamburg, Germany.
Expert Opin Drug Saf. 2009 May;8(3):305-15. doi: 10.1517/14740330902918273.
Allogeneic stem cell transplantation (allo-SCT) for haematological malignancies became a safer approach in recent years, for example, owing to improved supportive strategies. However, despite the efficacy of the procedure, morbidity and mortality mainly caused by infections and organ toxicity remain serious problems. Due to the variety of conditioning regimens being applied before allo-SCT, one important aspect is represented by the toxicity profiles of the specific compounds, which are being applied for the reduction of the leukaemia cell load and for immunosuppression. This is being illustrated by the hepatotoxic profile of busulfan with its high rate of veno-occlusive disease. However, recent advances in our understanding of drug metabolism, progress in the measurement of drug concentration, and the invention of some new drugs and therapeutic approaches in the conditioning period are promising steps in achieving more safety for patients undergoing allo-SCT. Reduced-intensity conditioning concepts allow the inclusion of heavily pretreated patients or patients with severe co-morbidities in transplantation concepts. New prophylactic regimens, including poly- or monoclonal antibodies, result in reduced rates of graft-versus-host disease, and some 'new' drugs such as treosulfan or clofarabine widen the range of available conditioning regimens for specific situations.
近年来,同种异体干细胞移植(allo-SCT)在血液恶性肿瘤的治疗中变得更加安全,例如,由于支持性策略的改进。然而,尽管该程序具有疗效,但发病率和死亡率主要由感染和器官毒性引起,仍然是严重的问题。由于 allo-SCT 前应用的预处理方案种类繁多,一个重要方面是特定化合物的毒性特征,这些化合物用于降低白血病细胞负荷和免疫抑制。白消安的肝毒性特征及其高静脉闭塞性疾病发生率就是一个例证。然而,我们对药物代谢的理解的最新进展、药物浓度测量的进展,以及在预处理期间发明的一些新药和治疗方法,是为接受 allo-SCT 的患者实现更高安全性的有希望的步骤。减强度预处理概念允许将大量预处理患者或患有严重合并症的患者纳入移植概念中。新的预防方案,包括多克隆或单克隆抗体,导致移植物抗宿主病的发生率降低,一些“新”药物,如曲奥舒凡或克拉屈滨,拓宽了特定情况下可用的预处理方案范围。