Dazzi F, Szydlo R M, Goldman J M
Department of Haematology, Hammersmith Hospital/ICSM, London, United Kingdom.
Exp Hematol. 1999 Oct;27(10):1477-86. doi: 10.1016/s0301-472x(99)00096-x.
The infusion of lymphocytes from the original marrow donor (donor lymphocyte infusion [DLI]) reinduces complete remission in a high percentage of patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplant, and thus, is probably the best initial approach to their management. The major predictive factor for response is the disease stage at time of treatment, because patients in molecular or cytogenetic relapse fare better than those in hematologic relapse. Moreover, patients with a short interval between transplant and DLI have a higher probability of response than those with longer intervals. The durability of DLI-induced remissions has not yet been established, but they appear to be prolonged. The observation that DLI can be highly effective for patients in relapse has encouraged the recent development of new strategies designed to minimize the myeloablative regimen and exploit the immunotherapeutic component of the transplant. The principal complication associated with use of DLI is the occurrence of graft-versus-host disease (GVHD). Several approaches have been tested to reduce the incidence or impact of GVHD, based on the ex vivo depletion of alloreactive donor cells or the use of donor T cells transduced with a suicide gene. The incidence of GVHD can also be reduced by starting with low doses of donor cells and "escalating" subsequent doses as required. However, the identification of selective targets for leukemia-reactive immunity is probably the optimal strategy to resolve the problem of GVHD. Although currently minor histocompatibility antigens appear to be the most likely targets for DLI, several groups are focusing on the generation of leukemia-specific immunity. The results obtained by use of tumor-associated antigens presented by dendritic cells are encouraging and may lay the foundations for the use of adoptive immunotherapy in the autologous setting.
输注来自原骨髓供体的淋巴细胞（供体淋巴细胞输注 [DLI]）可使高比例的异基因干细胞移植后复发的慢性髓性白血病（CML）患者再次完全缓解，因此，这可能是对其进行治疗的最佳初始方法。反应的主要预测因素是治疗时的疾病阶段，因为处于分子或细胞遗传学复发阶段的患者比血液学复发患者预后更好。此外，移植与 DLI 间隔时间短的患者比间隔时间长的患者反应概率更高。DLI 诱导缓解的持久性尚未确定，但似乎有所延长。DLI 对复发患者可能非常有效的这一观察结果，促使最近开发了新的策略，旨在尽量减少清髓方案并利用移植的免疫治疗成分。与使用 DLI 相关的主要并发症是移植物抗宿主病（GVHD）的发生。已经测试了几种方法来降低 GVHD 的发生率或影响，这些方法基于体外清除同种异体反应性供体细胞或使用转导了自杀基因的供体 T 细胞。通过开始使用低剂量供体细胞并根据需要“递增”后续剂量，也可以降低 GVHD 的发生率。然而，确定白血病反应性免疫的选择性靶点可能是解决 GVHD 问题的最佳策略。虽然目前次要组织相容性抗原似乎是 DLI 最可能的靶点，但几个研究小组正专注于产生白血病特异性免疫。使用树突状细胞呈递的肿瘤相关抗原所获得的结果令人鼓舞，可能为在自体环境中使用过继性免疫疗法奠定基础。
