Laboratory of Translational Immunology and.
Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, The Netherlands.
Blood. 2016 Dec 8;128(23):2607-2615. doi: 10.1182/blood-2016-06-724005. Epub 2016 Oct 3.
T-cell immune reconstitution (IR) after allogeneic hematopoietic cell transplantation (allo-HCT) is highly variable between patients and may take several months to even years. Patients with delayed or unbalanced T-cell IR have a higher probability of developing transplantation-related morbidity, mortality, and relapse of disease. Hence, there is a need for strategies to better predict and improve IR to reduce these limitations of allo-HCT. In this review, we provide an update of current and in-near-future clinically relevant strategies before, during, and after transplantation to achieve successful T-cell IR. Potent strategies are choosing the right HCT source (eg, donor-recipient matching, cell dose, graft manipulation), individualized conditioning and serotherapy (eg, antithymocyte globulin), nutritional status, exercise, home care, modulation of microbiota, enhancing homeostatic peripheral expansion, promoting thymopoiesis, and the use of adjuvant-targeted cellular immunotherapies. Strategies to prevent graft-versus-host disease are important as well because this complication and the subsequent need for immunosuppression affects T-cell IR and function. These options aim for personalized precision transplantation, where allo-HCT therapy is designed to boost a well-balanced T-cell IR and limit complications in individual patients, resulting in overall lower morbidity and higher survival chances.
异基因造血细胞移植 (allo-HCT) 后 T 细胞免疫重建 (IR) 在患者之间差异很大，可能需要数月甚至数年时间。T 细胞 IR 延迟或失衡的患者发生移植相关发病率、死亡率和疾病复发的可能性更高。因此，需要有策略来更好地预测和改善 IR，以降低 allo-HCT 的这些局限性。在这篇综述中，我们提供了当前和即将出现的与临床相关的策略，这些策略在移植前、移植期间和移植后用于实现成功的 T 细胞 IR。有力的策略包括选择合适的 HCT 来源（例如，供受者匹配、细胞剂量、移植物处理）、个体化的预处理和血清疗法（例如，抗胸腺细胞球蛋白）、营养状况、运动、家庭护理、调节微生物群、促进外周稳态扩增、促进胸腺生成，以及使用辅助靶向细胞免疫疗法。预防移植物抗宿主病的策略也很重要，因为这种并发症以及随后的免疫抑制需求会影响 T 细胞 IR 和功能。这些选择旨在实现个性化的精确移植，使 allo-HCT 治疗能够促进平衡的 T 细胞 IR，并在个体患者中限制并发症，从而总体降低发病率并提高生存率。
