减低强度预处理的异基因造血干细胞移植拯救性治疗难治性白血病

 讨论减低强度预处理的异基因造血干细胞移植（RIC-HSCT）治疗难治性白血病的治疗时机和病例选择、预处理方案设计、移植后嵌合状态监测、移植物抗宿主病等问题。已经有越来越多的学者认为,对于难治性白血病患者,不应以牺牲患者的整体状况为代价,强求在完全缓解状态下进行造血干细胞移植。RIC-HSCT的本质属于一种过继性免疫治疗,所以必须考虑到免疫攻击的靶点和免疫反应的潜伏期。相对缺乏免疫攻击靶点和生长过快的肿瘤可能难以用RIC-HSCT控制。RIC-HSCT目前并无统一的预处理方案,但是对于难治复发白血病患者,预处理剂量的强度起着十分重要的作用,很多研究者采用了介于"非清髓"的剂量标准和传统清髓方案之间的剂量。RIC-HSCT早期往往难以达到完全供者嵌合。稳定的完全供者嵌合状态以发挥移植物抗白血病（GVL）效应清除微小残留病变,是确保患者长期生存的关键,故建议对于采用RIC-HSCT的患者,应当采用敏感的方法（如聚合酶链反应检测短串联重复序列,PCR-STR）更频繁的（2～4周）监测移植后嵌合状态,并应当对特异的细胞系列进行检测（如T细胞）。同传统移植相比,RIC-HSCT时急性和慢性移植物抗宿主病（GVHD）的发生率是相似的。GVHD的发生同GVL效应有相关性,早期减、停免疫抑制剂和供者淋巴细胞输注,可以促进向完全供者嵌合状态的转化,可能对于预防未缓解期行RIC-HSCT的白血病患者复发有一定益处,但最大的并发症就是诱发GVHD。

Allogeneic hematopoietic stem cell transplantation following reduced intensity conditioning regimen as salvage therapy for refractory leukemia

Several hot questions such as selection of patients and favorable time of transplantation, design of conditioning regimen, monitoring of chimerism and complication of graft versus host disease (GVHD) in allogeneic hematopoietic stem cell transplantation following reduced intensity regimen (RIC-HSCT) as salvage therapy for refractory leukemia are discussed in this article. More and more investigators began to recognize that it was not a fundamental to undergo transplantation in complete remission for patients with refractory leukemia, since it may expend patients' physical status. RIC-HSCT may be substantially considered as a kind of adoptive immunotherapy, so that immunologic attacking targets and the latency of immunoreactian must be considered when making the decision to use, lacking of attacking targets and rapidly growing diseases seemed to be less susceptible to control. Commonly used reduced intensity regimens differed significantly, but it was clear that dose intensity was very important in refractory leukemia. In fact, many investigators used intermediate dosage between criteria of "non-myeloablative" and conventional myeloablative regimens. Complete donor chimerism is the hallmark of engraftment but often delayed in RIC-HSCT. Since sustained complete donor chimerism induced persistent graft-versus-leukemia (GVL) effect play an important role in patients' long-term survival, it was recommended that sensitive techniques (eg. STR-PCR) should be used to analysis chimerism and should be measured more frequently (every 2-4 weeks), and lineage-specific chimerism (eg. T cell) analysis was also recommended. As compared with traditional HSCT, the incidences of acute and chronic GVHD are similar and the onset of GVHD is associated with the GVL effect. Decrease or interruption of immunosuppressive drugs early after transplantation and donor lymphocyte infusion may facilitate transformation to complete donor chimerism, so that it may benefit patients with advanced disease at time of transplantation from avoiding disease relapse in one hand, but may induce GVHD in the other hand.