Department of Pediatrics, Seattle Children's Hospital Cancer and Blood Disorders Service, University of Washington School of Medicine, Seattle, Washington, USA.
Department of Population and Public Health Sciences, University of Southern California, Los Angels, California, USA.
Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30584. doi: 10.1002/pbc.30584. Epub 2023 Jul 21.
During the past decade, the outcomes of pediatric patients with acute myeloid leukemia (AML) have plateaued with 5-year event-free survival (EFS) and overall survival (OS) of approximately 46 and 64%, respectively. Outcomes are particularly poor for those children with high-risk disease, who have 5-year OS of 46%. Substantial survival improvements have been observed for a subset of patients treated with targeted therapies. Specifically, children with KMT2A-rearranged AML and/or FLT3 internal tandem duplication (FLT3-ITD) mutations benefitted from the addition of gemtuzumab ozogamicin, an anti-CD33 antibody-drug conjugate, in the AAML0531 clinical trial (NCT00372593). Sorafenib also improved response and survival in children with FLT3-ITD AML in the AAML1031 clinical trial (NCT01371981). Advances in characterization of prognostic cytomolecular events have helped to identify patients at highest risk of relapse and facilitated allocation to consolidative hematopoietic stem cell transplant (HSCT) in first remission. Some patients clearly have improved survival with HSCT, although the benefit is largely unknown for most patients. Finally, data-driven refinements in supportive care recommendations continue to evolve with meaningful and measurable reductions in toxicity and improvements in EFS and OS. As advances in application of targeted therapies, risk stratification, and improved supportive care measures are incorporated into current trials and become standard-of-care, there is every expectation that we will see improved survival with a reduction in toxic morbidity and mortality. The research agenda of the Children's Oncology Group's Myeloid Diseases Committee continues to build upon experience and outcomes with an overarching goal of curing more children with AML.
在过去的十年中，儿科急性髓系白血病（AML）患者的治疗结果已趋于稳定，无事件生存率（EFS）和总生存率（OS）分别约为 46%和 64%。对于患有高危疾病的儿童，预后尤其不佳，其 5 年 OS 为 46%。针对某些患者采用靶向治疗，已观察到显著的生存改善。具体而言，在 AAML0531 临床试验（NCT00372593）中，接受 KMT2A 重排 AML 和/或 FLT3 内部串联重复（FLT3-ITD）突变的儿童，联合应用抗 CD33 抗体药物偶联物吉妥珠单抗，获益明显。在 AAML1031 临床试验（NCT01371981）中，索拉非尼也改善了伴有 FLT3-ITD AML 儿童的反应和生存。对预后细胞分子事件的特征进行深入研究，有助于识别复发风险最高的患者，并有助于在首次缓解时进行巩固性造血干细胞移植（HSCT）。一些患者接受 HSCT 后明显提高了生存率，但大多数患者的获益尚不清楚。最后，支持性治疗建议的数据驱动式改进继续发展，毒性明显降低，EFS 和 OS 得到改善。随着靶向治疗、风险分层和改进的支持性治疗措施的应用进展，纳入当前试验并成为标准治疗方法，我们有望看到生存改善，同时降低毒性发病率和死亡率。儿童肿瘤学组髓系疾病委员会的研究议程将继续在经验和结果的基础上进行，其总体目标是治愈更多的 AML 患儿。
