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自体造血干细胞移植治疗慢性淋巴细胞白血病——仍是有效治疗选择,还是游戏结束?

Autologous Stem Cell Transplantation for Chronic Lymphocytic Leukemia - Still a Valid Treatment Option, or is the Game Over?

机构信息

Department of Medicine V, University of Heidelberg, Heidelberg, Germany ; Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary, University of London, London, UK.

出版信息

Mediterr J Hematol Infect Dis. 2012;4(1):e2012071. doi: 10.4084/MJHID.2012.071. Epub 2012 Nov 6.

Abstract

Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) has been established as the current standard of care for young and fit patients with chronic lymphocytic leukemia (CLL). In the early nineties of the last century, long before the advent of fludarabine or antibody-based strategies, there was realistic hope that myeloablative therapy followed by autologous stem cell transplantation (autoSCT) might be an effective and potentially curative front-line treatment option for suitable patients with CLL. Since then, several prospective trials have disenthralled this hope: although autoSCT can prolong event and progression-free survival if used as part of early front-line treatment, it does not improve overall survival, while it is associated with an increased risk of late adverse events such as secondary malignancies. In addition, autoSCT lacks the potential to overcome the negative impact of biomarkers that confer resistance to chemotherapy or early relapse. The role of autoSCT has also been explored in the context of FCR, and it was demonstrated that its effect is inferior to the currently established optimal treatment regimen. In view of ongoing attempts to improve on FCR, promising clinical activity of new substances even in relapsed/ refractory CLL patients, exciting novel cell therapy approaches and advantages in the understanding of the disease and detection of Minimal Residual Disease (MRD), autoSCT has lost its place as a standard treatment option for CLL.

摘要

氟达拉滨、环磷酰胺和利妥昔单抗(FCR)的化疗免疫治疗已被确立为年轻和健康的慢性淋巴细胞白血病(CLL)患者的当前标准治疗方法。在上世纪 90 年代初,远在氟达拉滨或基于抗体的策略出现之前,人们曾有过切实的希望,即清髓性治疗后进行自体干细胞移植(autoSCT)可能是适合的 CLL 患者的一种有效且潜在的治愈性一线治疗选择。从那时起,几项前瞻性试验已经消除了这种希望:尽管 autoSCT 可作为早期一线治疗的一部分延长事件和无进展生存期,但它不能改善总体生存率,并且与晚期不良事件(如继发性恶性肿瘤)的风险增加相关。此外,autoSCT 缺乏克服赋予化疗耐药性或早期复发的生物标志物的负面影响的潜力。在 FCR 的背景下也探索了 autoSCT 的作用,结果表明其效果不如目前确立的最佳治疗方案。鉴于正在努力改进 FCR,新药物即使在复发/难治性 CLL 患者中也具有有希望的临床活性、令人兴奋的新型细胞治疗方法以及在疾病理解和最小残留疾病(MRD)检测方面的优势,autoSCT 已不再是 CLL 的标准治疗选择。

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Autografting CLL: the game is over!慢性淋巴细胞白血病的自体移植:游戏结束!
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