Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.
German Cancer Consortium (DKTK) partner site, Freiburg, Germany.
Ann Hematol. 2020 Jul;99(7):1551-1560. doi: 10.1007/s00277-020-04082-7. Epub 2020 Jun 6.
TP53 aberrations reportedly predict favorable responses to decitabine (DAC) in acute myeloid leukemia (AML). We evaluated clinical features and outcomes associated with chromosome 17p loss or TP53 gene mutations in older, unfit DAC-treated AML patients in a phase II trial. Of 178 patients, 25 had loss of 17p in metaphase cytogenetics; 24 of these had a complex (CK+) and 21 a monosomal karyotype (MK+). In analyses in all patients and restricted to CK+ and MK+ patients, 17p loss tended to associate with higher rates of complete remission (CR), partial remission (PR), or antileukemic effect (ALE). Despite favorable response rates, there was no significant OS difference between patients with or without loss of 17p in the entire cohort or in the CK+ and MK+ cohort. TP53 mutations were identified in eight of 45 patients with material available. Five of the eight TP53-mutated patients had 17p loss. TP53-mutated patients had similar rates of CR/PR/ALE but shorter OS than those with TP53 wild type (P = 0.036). Moreover, patients with a subclone based on mutation data had shorter OS than those without (P = 0.05); only one patient with TP53-mutated AML had a subclone. In conclusion, 17p loss conferred a favorable impact on response rates, even among CK+ and MK+ patients that however could not be maintained. The effect of TP53 mutations appeared to be different; however, patient numbers were low. Future research needs to further dissect the impact of the various TP53 aberrations in HMA-based combination therapies. The limited duration of favorable responses to HMA treatment in adverse-risk genetics AML should prompt physicians to advance allografting for eligible patients in a timely fashion.
据报道，TP53 异常可预测急性髓系白血病（AML）患者对去甲基化药物（DAC）的反应良好。我们在一项 II 期临床试验中评估了染色体 17p 缺失或 TP53 基因突变与老年、不适合 DAC 治疗的 AML 患者的临床特征和结局的关系。在 178 例患者中，25 例在中期细胞遗传学中有 17p 缺失；其中 24 例为复杂核型（CK+），21 例为单倍体核型（MK+）。在所有患者的分析中以及在 CK+和 MK+患者的分析中，17p 缺失倾向于与更高的完全缓解（CR）、部分缓解（PR）或抗白血病效应（ALE）率相关。尽管缓解率较高，但在整个队列或 CK+和 MK+队列中，有或没有 17p 缺失的患者的总生存期（OS）没有显著差异。在有材料的 45 例患者中，鉴定出 8 例 TP53 突变。8 例 TP53 突变患者中有 5 例存在 17p 缺失。TP53 突变患者的 CR/PR/ALE 率相似，但 OS 短于 TP53 野生型患者（P=0.036）。此外，基于突变数据存在亚克隆的患者 OS 短于没有亚克隆的患者（P=0.05）；仅有 1 例 TP53 突变型 AML 患者存在亚克隆。总之，17p 缺失对反应率有有利影响，即使在 CK+和 MK+患者中也是如此，但无法维持。TP53 突变的影响似乎不同；然而，患者数量较少。未来的研究需要进一步剖析在基于 HMA 的联合治疗中各种 TP53 异常的影响。在具有不良遗传学风险的 AML 中，HMA 治疗的有利反应持续时间有限，这应促使医生及时为符合条件的患者推进同种异体移植。
