Reagan John L, Fast Loren D, Winer Eric S, Safran Howard, Butera James N, Quesenberry Peter J
Division of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medical School, Providence, RI 02903, USA.
Adv Hematol. 2012;2012:784213. doi: 10.1155/2012/784213. Epub 2012 Jan 18.
Much of the therapeutic benefit of allogeneic transplant is by a graft versus tumor effect. Further data shows that transplant engraftment is not dependant on myeloablation, instead relying on quantitative competition between donor and host cells. In the clinical setting, engraftment by competition alone is not feasible due to the need for large numbers of infused cells. Instead, low-level host irradiation has proven to be an effective engraftment strategy that is stem cell toxic but not myeloablative. The above observations served as the foundation for clinical trials utilizing allogeneic matched and haploidentical peripheral blood stem cell infusions with minimal conditioning in patients with refractory malignancies. Although engraftment was transient or not apparent, there were compelling responses in a heavily pretreated patient population that appear to result from the breaking of tumor immune tolerance by the host through the actions of IFNγ, invariant NK T cells, CD8 T cells, NK cells, or antigen presenting cells.
同种异体移植的大部分治疗益处来自移植物抗肿瘤效应。进一步的数据表明，移植植入并不依赖于清髓，而是依赖于供体细胞和宿主细胞之间的定量竞争。在临床环境中，由于需要大量输注细胞，仅靠竞争实现植入是不可行的。相反，低剂量宿主照射已被证明是一种有效的植入策略，它对干细胞有毒性，但不会造成清髓。上述观察结果为利用同种异体匹配和单倍体相合外周血干细胞输注、对难治性恶性肿瘤患者进行最小预处理的临床试验奠定了基础。尽管植入是短暂的或不明显的，但在经过大量预处理的患者群体中出现了令人信服的反应，这似乎是由于宿主通过IFNγ、不变自然杀伤T细胞、CD8 T细胞、自然杀伤细胞或抗原呈递细胞的作用打破了肿瘤免疫耐受所致。
