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Abstract：
Hematopoietic stem cell transplantation (HCT) is a curative intervention in non-malignant disorders (NMD) that benefit from donor-derived hematopoiesis, immunity, and establishment of vital cells or enzyme systems. Stability or reversal of disease symptoms depends on adequacy and long-term stability of donor cell engraftment in the compartment of interest. Unlike hematologic malignancies where complete replacement with donor derived hematopoiesis is desirable for a cure, NMD manifestations can often be controlled in the presence of mixed chimerism. This allows for exploration of reduced intensity conditioning regimens that can limit organ toxicity, late effects, and increase tolerability especially in young recipients or those with a large burden of disease related morbidity. However, the levels of donor chimerism conducive to disease control vary between NMD, need to focus on the hematopoietic lineage necessary to correct individual disorders, and need to be assessed for stability over time, i.e., a whole lifespan. An enhanced ability to reject grafts due to recipient immune competence, alloimmunization, and autoimmunity add to the complexity of this balance making NMD a highly diverse group of unrelated disorders. The addition of donor factors such as stem cell source and Human-Leukocyte-Antigen match extend the complexity such that \'one size does not fit all\'. In this perspective, we will discuss current knowledge of the role of chimerism and goals, approach to HCT, and emerging methods of boosting engraftment and graft function, and monitoring recommendations. We draw attention to knowledge gaps and areas of necessity for further research and research support.
摘要：
造血干细胞移植（HCT）是对非恶性疾病（NMD）的治疗性干预，受益于供体来源的造血，豁免权,和建立重要的细胞或酶系统。疾病症状的稳定性或逆转取决于供体细胞移植在目标区室中的充分性和长期稳定性。与血液恶性肿瘤不同，在血液恶性肿瘤中，需要用供体衍生的造血功能进行完全替代，NMD表现通常可以在混合嵌合体存在的情况下得到控制。这允许探索可以限制器官毒性的降低强度的调节方案，后期效应,并增加耐受性，特别是在年轻的接受者或那些与疾病相关的发病率负担很大的人。然而,有助于疾病控制的供体嵌合体水平因NMD而异，需要关注纠正个体疾病所必需的造血谱系，需要评估一段时间的稳定性，即，整个寿命。由于受体免疫能力的增强拒绝移植物的能力，同种免疫,自身免疫增加了这种平衡的复杂性，使NMD成为高度多样化的无关疾病组。诸如干细胞来源和人-白细胞-抗原匹配的供体因子的添加扩展了复杂性,使得“一个尺寸不适合所有”。从这个角度来看,我们将讨论嵌合体和目标的作用的当前知识，HCT的方法，以及增强移植和移植功能的新兴方法，监测建议。我们提请注意知识差距和需要进一步研究和研究支持的领域。
