Over the last decade, the development of multiple strategies to allow the safe transfer from the donor to the patient of high numbers of partially HLA-incompatible T cells has dramatically reduced the toxicities of haploidentical hematopoietic cell transplantation (haplo-HCT), but this was not accompanied by a similar positive impact on the incidence of post-transplantation relapse. In the present review, we will elaborate on how the unique interplay between HLA-mismatched immune system and malignancy that characterizes haplo-HCT may impact relapse biology, shaping the selection of disease variants that are resistant to the “graft-vs.-leukemia” effect. In particular, we will present current knowledge on genomic loss of HLA, a relapse modality first described in haplo-HCT and accounting for a significant proportion of relapses in this setting, and discuss other more recently identified mechanisms of post-transplantation immune evasion and relapse, including the transcriptional downregulation of HLA class II molecules and the enforcement of inhibitory checkpoints between T cells and leukemia. Ultimately, we will review the available treatment options for patients who relapse after haplo-HCT and discuss on how a deeper insight into relapse immunobiology might inform the rational and personalized selection of therapies to improve the largely unsatisfactory clinical outcome of relapsing patients.

在过去的十年中，开发了多种策略以允许将大量部分HLA不相容的T细胞从供体安全转移至患者，从而大大降低了单倍型造血细胞移植（haplo-HCT）的毒性。对移植后复发的发生率没有类似的积极影响。在本综述中，我们将详细阐述HLA错配的免疫系统与恶性肿瘤之间的独特相互作用（其特征是单倍型HCT）可能如何影响复发生物学，从而影响对“移植物抗白血病”的疾病变异的选择。影响。特别是，我们将介绍有关HLA基因组丢失的最新知识，这是haplo-HCT中首先描述的一种复发方式，并说明了这种情况下复发的重要比例，并讨论了移植后免疫逃逸和复发的其他​​最近发现的机制，包括HLA II类分子的转录下调和T细胞与白血病之间抑制性检查点的实施。最终，我们将回顾单倍HCT后复发患者的可用治疗方案，并讨论对复发免疫生物学的更深入了解如何为合理和个性化的治疗选择提供信息，从而改善复发患者的大部分临床效果。