Abstract：
BACKGROUND: Adult acute myeloid leukaemia (AML) patients with complex karyotype (CK) generally have unfavourable outcomes. CK commonly co-exists with characteristic chromosomal and genetic abnormalities such as monosomal karyotype (MK), -17 or 17p- [abn(17p)] and TP53 mutations. Their individual prognostic significance needs to be clarified.
METHODS: Seventy-three adult CK-AML patients and eleven adult non-CK-AML patients with TP53 mutations (non-CK/TP53mu ) who were diagnosed and received therapy at our institute were enrolled. One hundred and fifty-seven AML cases retrieved from the cancer genome atlas (TCGA) for validation.
RESULTS: Among CK-AML patients, those with TP53 mutations (CK/TP53mu ) had significantly lower rates of 1-course induction complete remission (CR), 2-year relapse-free survival (RFS) and 2-year overall survival (OS) than those without TP53 mutations (CK/TP53wt ); whereas, abn(17p) did not have the above impacts; MK was significantly associated with a lower 2-year OS rate but was not related to the rates of CR and RFS. Multivariate analysis showed that it were TP53 mutations and treating with chemotherapy alone but not MK and abn(17p) that independently predicted the adverse prognosis for RFS and OS in CK-AML. Furthermore, non-CK/TP53mu patients showed similar rates of CR, RFS and OS to CK/TP53mu patients. Validation using the TCGA cohort showed that CK/TP53mu patients had a significantly lower 2-year OS rate than CK/TP53wt patients, whereas abn(17p) and MK did not impact OS; the 2-year OS rate of patients with CK/TP53wt was similar to that of patients with intermediate-risk cytogenetics.
CONCLUSIONS: Adult CK-AML patients have varied risks and TP53 mutations seem to be an independent adverse prognostic factor.
METHODS: Seventy-three adult CK-AML patients and eleven adult non-CK-AML patients with TP53 mutations (non-CK/TP53mu ) who were diagnosed and received therapy at our institute were enrolled. One hundred and fifty-seven AML cases retrieved from the cancer genome atlas (TCGA) for validation.
RESULTS: Among CK-AML patients, those with TP53 mutations (CK/TP53mu ) had significantly lower rates of 1-course induction complete remission (CR), 2-year relapse-free survival (RFS) and 2-year overall survival (OS) than those without TP53 mutations (CK/TP53wt ); whereas, abn(17p) did not have the above impacts; MK was significantly associated with a lower 2-year OS rate but was not related to the rates of CR and RFS. Multivariate analysis showed that it were TP53 mutations and treating with chemotherapy alone but not MK and abn(17p) that independently predicted the adverse prognosis for RFS and OS in CK-AML. Furthermore, non-CK/TP53mu patients showed similar rates of CR, RFS and OS to CK/TP53mu patients. Validation using the TCGA cohort showed that CK/TP53mu patients had a significantly lower 2-year OS rate than CK/TP53wt patients, whereas abn(17p) and MK did not impact OS; the 2-year OS rate of patients with CK/TP53wt was similar to that of patients with intermediate-risk cytogenetics.
CONCLUSIONS: Adult CK-AML patients have varied risks and TP53 mutations seem to be an independent adverse prognostic factor.
摘要：
背景：具有复杂核型（CK）的成人急性髓系白血病（AML）患者通常具有不利的结局。CK通常与特征性染色体和遗传异常共存，如单体核型（MK），-17或17p-[abn(17p)]和TP53突变。它们的个体预后意义需要澄清。
方法：纳入了在我们研究所诊断并接受治疗的73例成人CK-AML患者和11例有TP53突变（非CK/TP53mu）的成人非CK-AML患者。从癌症基因组图谱（TCGA）中检索到的157例AML病例进行验证。
结果：在CK-AML患者中，具有TP53突变（CK/TP53mu）的1个疗程诱导完全缓解（CR）的比率显着降低，2年无复发生存率（RFS）和2年总生存率（OS）比那些没有TP53突变（CK/TP53wt）;然而，abn（17p）没有上述影响；MK与较低的2年OS率显着相关，但与CR和RFS率无关。多因素分析表明，TP53突变和单独化疗而非MK和abn（17p）独立预测CK-AML的RFS和OS的不良预后。此外，非CK/TP53mu患者的CR率相似，对CK/TP53mu患者的RFS和OS。使用TCGA队列的验证显示，CK/TP53mu患者的2年OS率明显低于CK/TP53wt患者，而abn(17p)和MK不影响OS;CK/TP53wt患者的2年OS率与中危细胞遗传学患者相似.
结论：成人CK-AML患者具有不同的风险，TP53突变似乎是一个独立的不良预后因素。
方法：纳入了在我们研究所诊断并接受治疗的73例成人CK-AML患者和11例有TP53突变（非CK/TP53mu）的成人非CK-AML患者。从癌症基因组图谱（TCGA）中检索到的157例AML病例进行验证。
结果：在CK-AML患者中，具有TP53突变（CK/TP53mu）的1个疗程诱导完全缓解（CR）的比率显着降低，2年无复发生存率（RFS）和2年总生存率（OS）比那些没有TP53突变（CK/TP53wt）;然而，abn（17p）没有上述影响；MK与较低的2年OS率显着相关，但与CR和RFS率无关。多因素分析表明，TP53突变和单独化疗而非MK和abn（17p）独立预测CK-AML的RFS和OS的不良预后。此外，非CK/TP53mu患者的CR率相似，对CK/TP53mu患者的RFS和OS。使用TCGA队列的验证显示，CK/TP53mu患者的2年OS率明显低于CK/TP53wt患者，而abn(17p)和MK不影响OS;CK/TP53wt患者的2年OS率与中危细胞遗传学患者相似.
结论：成人CK-AML患者具有不同的风险，TP53突变似乎是一个独立的不良预后因素。
