Medical Department III, University Hospital Großhadern, Ludwig-Maximilians-University.
Department of Hematology and Oncology, Universitäts-Klinikum Augsburg, Augsburg, Germany.
J Immunother. 2022;45(2):104-118. doi: 10.1097/CJI.0000000000000404.
Allogeneic stem cell transplantation (alloSCT) is the treatment of choice for many patients with acute myeloid leukemia (AML) and myelodysplastic syndrome. The presentation of leukemic or allospecific antigens by malignant blasts is regarded as a crucial trigger for an effective allogeneic immune response. Conversely, insufficient stimulatory capacity by the leukemic blasts is thought to be a relevant escape mechanism from cellular immunotherapy (alloSCT). Our purpose was to test, whether the ability of malignant blasts to differentiate in vitro toward dendritic cells of leukemic origin (DCleu) is associated with clinical outcome. We isolated leukemic blasts from peripheral blood or bone marrow of AML and myelodysplastic syndrome patients before alloSCT (n=47) or at relapse after alloSCT (n=22). A panel of 6 different assays was used to generate DCleu in vitro. Results were correlated with clinical outcome. DCleu could be generated from all 69 samples. Significantly higher mean frequencies of DCleu were found in clinical long-term responders versus nonresponders to SCT (76.8% vs. 58.8%, P=0.006). Vice versa, the chance for response to SCT was significantly higher, if a DCleu+/dendritic cells (DC) ratio of >50% could be reached in vitro (P=0.004). Those patients were characterized by a longer time to relapse (P=0.04) and by a higher probability for leukemia-free survival (P=0.005). In vitro generation of DC and DCleu from leukemic blasts correlated with the clinical outcome. This observation may support a role of leukemic antigen presentation by "leukemia-derived DC" for the stimulation of an allogeneic immune response in AML.
异基因造血干细胞移植（alloSCT）是许多急性髓系白血病（AML）和骨髓增生异常综合征患者的首选治疗方法。恶性细胞通过表达白血病或同种异体抗原被认为是引发有效同种异体免疫反应的关键触发因素。相反，白血病细胞刺激能力不足被认为是逃避细胞免疫治疗（alloSCT）的一种相关机制。我们的目的是检测恶性细胞在体外向白血病来源的树突状细胞（DCleu）分化的能力是否与临床结果相关。我们在 alloSCT 前（n=47）或 alloSCT 后复发时（n=22）从 AML 和骨髓增生异常综合征患者的外周血或骨髓中分离出白血病细胞。使用 6 种不同的检测方法来体外生成 DCleu。结果与临床结果相关。从 69 个样本中都可以生成 DCleu。临床长期反应者的 DCleu 频率明显高于无反应者（76.8%比 58.8%，P=0.006）。相反，如果在体外达到 DCleu+/树突状细胞（DC）比率>50%，则对 SCT 有反应的机会明显更高（P=0.004）。这些患者的特点是复发时间更长（P=0.04），无白血病生存的概率更高（P=0.005）。白血病细胞在体外生成 DC 和 DCleu 与临床结果相关。这一观察结果可能支持“白血病来源的 DC”通过表达白血病抗原来刺激 AML 中的同种异体免疫反应的作用。
