PDF(Pubmed)
Abstract：
TP 53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are among the most lethal malignancies, characterized by dismal outcomes with currently available therapies. Allogeneic hematopoietic cell transplantation (allo-HCT) is widely thought to be the only treatment option to offer durable disease control. However, outcomes with allo-HCT in this context are quite poor, calling into question the utility of transplantation. In this review, we summarize the latest data on allo-HCT outcomes in this subgroup, evaluating the limitations of available evidence; we review the molecular heterogeneity of this disease, delineating outcomes based on distinct biological features to aid in patient selection; and we critically examine whether allo-HCT should be routinely applied in this disease on the basis of currently available data. We propose that the exceptionally poor outcomes of patients with TP53-mutated MDS/AML with biallelic loss and/or adverse-risk cytogenetics should motivate randomized-controlled trials of HCT vs non-HCT to determine whether transplantation can prolong survival and/or positively impact other clinically relevant outcomes such as patient-reported outcomes or healthcare resource utilization in this disease subset. Without dedicated prospective randomized trials, selecting who may actually derive benefit from allo-HCT for TP53-mutated MDS/AML can be described as ambiguous guesswork and must be carefully contemplated.
摘要：
■TP53突变的骨髓增生异常综合征（MDS）和急性髓细胞性白血病（AML）是最致命的恶性肿瘤，其特点是目前可用的治疗结果令人沮丧。异基因造血细胞移植(allo-HCT)被广泛认为是提供持久疾病控制的唯一治疗选择。然而,在这种情况下，allo-HCT的结果相当差，质疑移植的效用。在这次审查中,我们总结了这个亚组的allo-HCT结局的最新数据，评估现有证据的局限性；我们回顾了这种疾病的分子异质性，根据不同的生物学特征描述结局,以帮助患者选择;我们根据现有数据,严格检查allo-HCT是否应常规应用于该疾病.我们建议，TP53突变的MDS/AML患者具有双等位基因丢失和/或不良风险细胞遗传学的异常不良结果应激发HCT与非HCT的随机对照试验，以确定移植是否可以延长生存期和/或积极影响其他临床相关结果，例如患者报告的结果或该疾病子集的医疗资源利用。没有专门的前瞻性随机试验，选择可能从TP53突变的MDS/AML的allo-HCT中实际获益的人可以被描述为模棱两可的猜测,必须仔细考虑.
