Porter D L, Antin J H
Hematol Oncol Clin North Am. 1998 Feb;12(1):123-50. doi: 10.1016/s0889-8588(05)70500-1.
Until recently, the only curative therapy for patients with chronic myelogenous leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT) has been second allogeneic BMT. Recently, donor mononuclear cells have been given to patients with relapsed CML to induce a potent graft-versus-leukemia reaction and re-establish complete remissions in the majority of patients without the need for a second transplant. The extraordinary success of donor mononuclear cell infusions shows that it is possible to manipulate and harness the graft-versus-leukemia (GVL) reaction for clinical benefit. The identity of the effector cells and target antigens is unclear, but intensive investigation is beginning to define the complex cytokine and cellular interactions that mediate GVL reactivity. Current clinical trials are investigating strategies that will retain and enhance the GVL effects while limiting toxicity from this therapy. Ultimately, the ability to harness the GVL potential of allogeneic donor cells without excessive toxicity from graft-versus-host disease will be a central challenge in BMT and cellular immunotherapy.
直到最近，对于异基因骨髓移植（BMT）后复发的慢性粒细胞白血病（CML）患者，唯一的治愈性疗法仍是第二次异基因BMT。最近，已将供体单个核细胞给予复发的CML患者，以诱导强烈的移植物抗白血病反应，并使大多数患者在无需第二次移植的情况下重新实现完全缓解。供体单个核细胞输注的巨大成功表明，有可能操控并利用移植物抗白血病（GVL）反应以获得临床益处。效应细胞和靶抗原的特性尚不清楚，但深入研究已开始明确介导GVL反应性的复杂细胞因子和细胞间相互作用。目前的临床试验正在研究既能保留并增强GVL效应，又能限制该疗法毒性的策略。最终，在不产生过度移植物抗宿主病毒性的情况下利用异基因供体细胞的GVL潜能，将是BMT和细胞免疫疗法面临的核心挑战。
