CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Could (should) we abandon total body irradiation for conditioning in children with leukemia.
Could (should) we abandon total body irradiation for conditioning in children with leukemia.
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自数十年前开展造血细胞移植(HCT)以来,全身照射(TBI)一直用于清除患者正常和恶性造血细胞,再以HLA相合或不相合供者的干细胞重建造血。多年应用后,TBI的长期副作用已逐渐显现,在因急性淋巴细胞白血病(ALL)或急性髓系白血病(AML)接受异基因移植的低龄儿童中尤为明显。TBI的已知远期副作用包括继发恶性肿瘤,可显著损害患者在儿童期及成年后的生活质量。尽管近期一项大型随机研究显示了TBI预处理方案的获益,但TBI是否应从此成为所有ALL患儿的标准预处理方案,仍存在疑问。随着高灵敏度微小残留病(MRD)检测方法的引入,以及双特异性抗体或嵌合抗原受体(CAR)T细胞等新型免疫疗法与非TBI预处理方案结合,已经获得与TBI标准移植相当甚至更好的良好结果。本综述讨论多种已在研究及未来应在前瞻性试验中继续评估的方案,旨在避免儿童ALL患者接受TBI及其长期副作用。
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.
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