Truong Tony H, Jinca Cristian, Mann Georg, Arghirescu Smaranda, Buechner Jochen, Merli Pietro, Whitlock James A
Division of Pediatric Oncology, Blood and Marrow Transplant/Cellular Therapy, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
Department of Pediatrics, Victor Babeş University of Medicine and Pharmacy, Timişoara, Romania.
Front Pediatr. 2021 Dec 23;9:782785. doi: 10.3389/fped.2021.782785. eCollection 2021.
Pediatric acute lymphoblastic leukemia generally carries a good prognosis, and most children will be cured and become long-term survivors. However, a portion of children will harbor high-risk features at the time of diagnosis, have a poor response to upfront therapy, or suffer relapse necessitating more intensive therapy, which may include allogeneic hematopoietic stem cell transplant (HSCT). Recent advances in risk stratification, improved detection and incorporation of minimal residual disease (MRD), and intensification of upfront treatment have changed the indications for HSCT over time. For children in first complete remission, HSCT is generally reserved for those with the highest risk of relapse. These include patients with unfavorable features/cytogenetics who also have a poor response to induction and consolidation chemotherapy, usually reflected by residual blasts after prednisone or by detectable MRD at pre-defined time points. In the relapsed setting, children with first relapse of B-cell ALL are further stratified for HSCT depending on the time and site of relapse, while all patients with T-cell ALL are generally consolidated with HSCT. Alternatives to HSCT have also emerged over the last decade including immunotherapy and chimeric antigen receptor (CAR) T-cell therapy. These novel agents may spare toxicity while attempting to achieve MRD-negative remission in the most refractory cases and serve as a bridge to HSCT. In some situations, these emerging therapies can indeed be curative for some children with relapsed or resistant disease, thus, obviating the need for HSCT. In this review, we seek to summarize the role of HSCT in the current era of immunotherapy.
儿童急性淋巴细胞白血病总体预后良好，大多数儿童能够治愈并成为长期幸存者。然而，一部分儿童在诊断时会具有高危特征，对初始治疗反应不佳，或出现复发而需要更强化的治疗，这可能包括异基因造血干细胞移植（HSCT）。随着时间的推移，风险分层的进展、微小残留病（MRD）检测和纳入方法的改进以及初始治疗的强化改变了HSCT的适应证。对于首次完全缓解的儿童，HSCT通常保留给复发风险最高的患者。这些患者包括具有不良特征/细胞遗传学改变且对诱导和巩固化疗反应不佳的患者，通常表现为泼尼松治疗后仍有残留原始细胞或在预定义时间点可检测到MRD。在复发的情况下，B细胞急性淋巴细胞白血病首次复发的儿童根据复发时间和部位进一步分层以确定是否进行HSCT，而所有T细胞急性淋巴细胞白血病患者通常采用HSCT进行巩固治疗。在过去十年中，HSCT的替代方法也已出现，包括免疫疗法和嵌合抗原受体（CAR）T细胞疗法。这些新型药物在试图使最难治病例达到MRD阴性缓解的同时，可能避免毒性反应，并作为HSCT的桥梁。在某些情况下，这些新兴疗法确实可以治愈一些复发或耐药疾病的儿童，从而无需进行HSCT。在本综述中，我们旨在总结HSCT在当前免疫治疗时代的作用。
