Rettinger Eva, Heckl Dirk, Gibson Brenda, Sauer Martin, Turkiewicz Dominik, Kleinschmidt Katharina, Kalwak Krzysztof, Reinhardt Dirk, Locatelli Franco, Klusmann Jan-Henning
Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany.
Institute for Experimental Pediatric Hematology and Oncology (EPHO), Frankfurt, Germany.
Leukemia. 2025 Jul 9. doi: 10.1038/s41375-025-02685-5.
Allogeneic hematopoietic stem cell transplantation (HSCT) has significantly improved the outcome of children with high-risk (HR) acute myeloid leukemia (AML). Implementing allogeneic HSCT depends on numerous factors, including adverse cytogenetics, molecular abnormalities, poor response to first-line treatment, or relapsed or primary refractory disease. In HR AML, allogeneic HSCT is considered to be the consolidation strategy of choice in first complete remission (CR1) and offers the best chance of cure for patients with relapsed disease. Advances in donor/recipient typing, conditioning regimens, graft-versus-host-disease (GvHD) management, and supportive care have contributed to this improvement in overall-and transplant-outcome. This review will comprehensively discuss indications for HSCT and its modalities in pediatric AML by examining past, current, and future strategies for disease- and response-related stratification. We will examine the key importance of low/negative measurable residual disease (MRD) before transplantation and discuss conditioning regimens and graft variables, as well as novel approaches to harness the graft-versus-leukemia (GvL) effect, including targeted immunotherapy. The review will also address toxicities associated with HSCT, GvHD prophylaxis, and the management of treatment failure. Ultimately, this review seeks to inform clinical practice and highlights how improved outcomes have been achieved through the collective efforts of international study groups.
异基因造血干细胞移植（HSCT）显著改善了高危（HR）急性髓系白血病（AML）患儿的治疗结局。实施异基因HSCT取决于众多因素，包括不良细胞遗传学、分子异常、对一线治疗反应不佳、疾病复发或原发性难治性疾病。在HR AML中，异基因HSCT被认为是首次完全缓解（CR1）时的首选巩固策略，为复发患者提供了最佳治愈机会。供体/受体分型、预处理方案、移植物抗宿主病（GvHD）管理和支持治疗方面的进展促成了总体及移植结局的改善。本综述将通过审视过去、当前和未来与疾病及反应相关分层的策略，全面讨论小儿AML中HSCT的适应证及其方式。我们将探讨移植前低/阴性可测量残留病（MRD）的关键重要性，并讨论预处理方案和移植物变量，以及利用移植物抗白血病（GvL）效应的新方法，包括靶向免疫治疗。本综述还将讨论与HSCT相关的毒性、GvHD预防及治疗失败的管理。最终，本综述旨在为临床实践提供参考，并强调国际研究小组的共同努力是如何实现更好的治疗结局的。
