Children's University Hospital, University of Tuebingen, Germany.
Children's University Hospital, University of Tuebingen, Germany.
Blood Rev. 2022 Nov;56:100966. doi: 10.1016/j.blre.2022.100966. Epub 2022 Apr 22.
Total body irradiation (TBI) is used since the introduction of hematopoietic cell transplantation (HCT) decades ago to eradicate patients normal and malignant hematopoiesis prior to its replacement with stem cells from an HLA-matched or mismatched donor. Over the many years of its use, long-term side effects became obvious especially in younger pediatric patients who received an allogeneic transplantation for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). These long-term known side effects of TBI including the occurrence of second malignancies can significantly impair the quality of life of the patients either still during childhood and/or when they reach adulthood. Although the benefit of a TBI-based conditioning regimen has been shown recently in a large randomized study, concerns remain whether TBI should be from now on the standard conditioning regimen for all children with ALL. The introduction of sensitive methods for detection of minimal residual disease (MRD) and new immunotherapies using bispecific antibodies or chimeric antibody receptor (CAR) T-cells in combination with non-TBI-based conditioning regimens have shown already promising results comparable with the outcome after TBI-based standard transplants or even better. In this review, various approaches are discussed which have been and should further be investigated in prospective trials with the aim to avoid TBI and its long-term side effects in pediatric patients with ALL.
全身照射（TBI）自几十年前造血细胞移植（HCT）引入以来一直被用于在其被来自 HLA 匹配或不匹配供体的干细胞替代之前，消灭患者正常和恶性造血。在其使用的多年中，长期副作用变得明显，特别是在接受同种异体移植治疗急性淋巴细胞白血病（ALL）和急性髓系白血病（AML）的年轻儿科患者中。这些已知的 TBI 长期副作用，包括第二恶性肿瘤的发生，会显著影响患者的生活质量，无论是在儿童期还是成年期。尽管最近一项大型随机研究表明 TBI 为基础的预处理方案有获益，但仍有人担心 TBI 是否应该成为 ALL 所有儿童的标准预处理方案。使用双特异性抗体或嵌合抗原受体（CAR）T 细胞的微小残留病（MRD）的敏感检测方法和新免疫疗法的引入，结合非 TBI 为基础的预处理方案，已经显示出有前景的结果，与 TBI 为基础的标准移植后的结果相当，甚至更好。在这篇综述中，讨论了各种方法，这些方法已经并应在前瞻性试验中进一步研究，以避免 ALL 儿科患者的 TBI 及其长期副作用。
