Haroun Faysal, Solola Sade A, Nassereddine Samah, Tabbara Imad
George Washington University, 2150 Pennsylvania Ave. NW, Washington, DC, 20037, USA.
Drexel University College of Medicine, 2511 Queens Chapel rd NE, Washington, DC, 20018, USA.
Ann Hematol. 2017 Sep;96(9):1441-1448. doi: 10.1007/s00277-017-3051-5. Epub 2017 Jun 22.
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies. The rationale for the investigation of those agents in AML and MDS is supported by an observed increased expression of programmed cell death 1 protein (PD-1) and ligand 1 (PD-L1) in the hematopoietic microenvironment of AML and MDS, and its association with low TP53 and a poor prognosis. Early clinical experience in combination with a hypomethylating agent has shown encouraging responses; however, larger clinical trials are needed to determine the role of checkpoint inhibition in myeloid malignancies.
急性髓系白血病（AML）和骨髓增生异常综合征（MDS）是临床和分子层面异质性的克隆性髓系疾病，预后较差，尤其是在复发难治情况下以及60岁以上患者中。虽然异基因造血干细胞移植（ASCT）是一种潜在的治愈方法，但高复发率、发病率和死亡率使得有必要开发替代疗法。免疫检查点抑制剂可解除肿瘤免疫耐受，并已在治疗化疗耐药的血液系统和实体恶性肿瘤中显示出疗效。在AML和MDS中研究这些药物的理论依据是，在AML和MDS的造血微环境中观察到程序性细胞死亡1蛋白（PD-1）和配体1（PD-L1）表达增加，以及其与低TP53和不良预后的关联。与低甲基化药物联合使用的早期临床经验已显示出令人鼓舞的反应；然而，需要更大规模的临床试验来确定检查点抑制在髓系恶性肿瘤中的作用。
