Mielcarek Marco, Storb Rainer
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Leuk Lymphoma. 2005 Sep;46(9):1251-60. doi: 10.1080/10428190500125754.
Non-myeloablative preparative regimens have reduced regimen-related toxicities after allogeneic hematopoietic cell transplantation (HCT), which allows for the treatment of patients not eligible for myeloablative HCT. The reduced non-relapse mortality associated with non-myeloablative HCT is in part explained by the decreased incidence and severity of acute graft-vs-host disease (GVHD). Compared with conventional HCT, the onset of acute GVHD is delayed, and some patients may present with signs and symptoms characteristic of acute GVHD after day 100, in the absence of hallmarks of chronic GVHD. In contrast to the overall negative impact of acute GVHD on outcome, the net effects of chronic GVHD after non-myeloablative HCT appear to be beneficial, translating into improved progression-free survival among patients with different hematological malignancies. One obvious explanation for this beneficial effect is the strong association between chronic GVHD and protection against recurrent malignancy (graft-vs-tumor effect). Future strategies are aimed at reducing the risk of acute GVHD, in particular "early-onset" GVHD (before day 50), which is associated with increased non-relapse mortality and decreased overall survival, and at decreasing the corticosteroid dependence among patients who require immunosuppressive treatment for clinically established GVHD.
非清髓性预处理方案降低了异基因造血细胞移植(HCT)后与方案相关的毒性,这使得那些不符合清髓性HCT条件的患者也能接受治疗。与非清髓性HCT相关的非复发死亡率降低,部分原因是急性移植物抗宿主病(GVHD)的发生率和严重程度降低。与传统HCT相比,急性GVHD的发病延迟,一些患者可能在100天后出现急性GVHD的体征和症状,而没有慢性GVHD的特征。与急性GVHD对预后的总体负面影响相反,非清髓性HCT后慢性GVHD的净效应似乎是有益的,这转化为不同血液系统恶性肿瘤患者无进展生存期的改善。这种有益效应的一个明显解释是慢性GVHD与预防复发性恶性肿瘤(移植物抗肿瘤效应)之间的密切关联。未来的策略旨在降低急性GVHD的风险,特别是“早发性”GVHD(50天前),其与非复发死亡率增加和总生存期降低相关,同时降低那些因临床确诊的GVHD需要免疫抑制治疗的患者对皮质类固醇的依赖性。