Symons H J, Fuchs E J
Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
Bone Marrow Transplant. 2008 Sep;42(6):365-77. doi: 10.1038/bmt.2008.215. Epub 2008 Aug 4.
Hematopoietic SCT from a partially HLA-mismatched (HLA-haploidentical) first-degree relative offers the benefits of rapid and near universal donor availability but also the risks that result from traversing the HLA barrier; namely, graft failure, severe GVHD and prolonged immunodeficiency. Improvements over the last 10 years in conditioning regimens, graft engineering and pharmacological immunoprophylaxis of GVHD have substantially reduced the morbidity and mortality of HLA-haploidentical SCT. Highly immunosuppressive but nonmyeloablative conditioning extends the availability of HLA-haploidentical SCT to elderly hematologic malignancy patients lacking HLA-matched donors and permits recovery of autologous hematopoiesis in the event of graft failure. Current regimens for HLA-haploidentical SCT are associated with a 2-year non-relapse mortality of 20+/-5%, relapse of 35+/-15% and overall survival of 50+/-20%. Major developmental areas include harnessing natural killer cell alloreactivity to reduce the risk of disease relapse and improving immune reconstitution by delayed infusions of lymphocytes selectively depleted of alloreactive cells. Hematologic malignancy patients who lack suitably matched related or unrelated donors can now be treated with HLA-haploidentical related donor or unrelated umbilical cord blood SCT. Future clinical trials will assess the relative risks and benefits of these two graft sources.
来自部分人类白细胞抗原不匹配（HLA单倍型相同）的一级亲属的造血干细胞移植具有供体快速且几乎普遍可得的优势，但也存在跨越HLA屏障带来的风险，即移植物失败、严重移植物抗宿主病（GVHD）和长期免疫缺陷。在过去10年中，预处理方案、移植物工程和GVHD的药物免疫预防方面的改进已大幅降低了HLA单倍型相同造血干细胞移植的发病率和死亡率。高度免疫抑制但非清髓性预处理将HLA单倍型相同造血干细胞移植的适用范围扩大到缺乏HLA匹配供体的老年血液系统恶性肿瘤患者，并在移植物失败时允许自体造血恢复。目前HLA单倍型相同造血干细胞移植方案的2年无复发生存率为20±5%，复发率为35±15%，总生存率为50±20%。主要的发展领域包括利用自然杀伤细胞的同种异体反应性来降低疾病复发风险，以及通过延迟输注选择性去除同种异体反应性细胞的淋巴细胞来改善免疫重建。缺乏合适匹配的相关或无关供体的血液系统恶性肿瘤患者现在可以接受HLA单倍型相同的相关供体或无关脐血造血干细胞移植治疗。未来的临床试验将评估这两种移植物来源的相对风险和益处。
