Department of Medicine V, University of Heidelberg, Heidelberg, Germany.
Hematology Am Soc Hematol Educ Program. 2009:602-9. doi: 10.1182/asheducation-2009.1.602.
Efforts to develop curative treatment strategies for chronic lymphocytic leukemia (CLL) in recent years have focused on allogeneic stem cell transplantation (alloSCT). The crucial anti-leukemic principle of alloSCT in CLL appears to be the immune-mediated anti-host activities conferred with the graft (graft-versus-leukemia effects, GVL). Evidence for GVL in CLL is provided by studies analyzing the kinetics of minimal residual disease on response to immune modulation after transplantation, suggesting that GVL can result in complete and durable suppression of the leukemic clone. AlloSCT from matched related or unrelated donors can overcome the treatment resistance of poor-risk CLL, ie, purine analogue refractory disease and CLL with del 17p-. Even with reduced-intensity conditioning, alloSCT in CLL is associated with significant mortality and morbidity due to graft-versus-host disease, which has to be weighed against the risk of the disease when defining the indication for transplantation. Therefore, it can be regarded as a reasonable treatment option only for eligible patients who fulfill accepted criteria for poor-risk disease. If alloSCT is considered, it should be performed before CLL has advanced to a status of complete refractoriness to assure an optimum chance for a successful outcome. Prospective trials are underway to prove whether allo-SCT can indeed change the natural history of poor-risk CLL.
近年来,开发慢性淋巴细胞白血病 (CLL) 治疗方法的努力集中在异基因干细胞移植 (alloSCT) 上。alloSCT 在 CLL 中抗白血病的关键原则似乎是移植物赋予的免疫介导的抗宿主活性(移植物抗白血病效应,GVL)。在 CLL 中,GVL 的证据来自于分析移植后免疫调节反应中小残留疾病动力学的研究,表明 GVL 可以导致白血病克隆的完全和持久抑制。来自匹配的相关或无关供体的 alloSCT 可以克服 CLL 的治疗抵抗,即嘌呤类似物难治性疾病和 17p-缺失的 CLL。即使采用强度降低的预处理方案,alloSCT 在 CLL 中也与移植物抗宿主病的高死亡率和发病率相关,在定义移植适应症时,必须权衡疾病风险。因此,只有符合不良风险疾病公认标准的合格患者才能将其视为合理的治疗选择。如果考虑 alloSCT,则应在 CLL 发展到完全对治疗无反应之前进行,以确保成功的最佳机会。正在进行前瞻性试验以证明 allo-SCT 是否确实可以改变不良风险 CLL 的自然病程。