孔繁聪, 蔡少芬, 齐凌, 纪德香, 喻敏, 周玉兰, 王诗轩, 李菲. PTPN11基因突变对初治急性髓系白血病患者的预后影响及倾向性评分匹配分析[J]. 中国肿瘤临床, 2023, 50(18): 928-934. DOI: 10.12354/j.issn.1000-8179.2023.20230623
引用本文: 孔繁聪, 蔡少芬, 齐凌, 纪德香, 喻敏, 周玉兰, 王诗轩, 李菲. PTPN11基因突变对初治急性髓系白血病患者的预后影响及倾向性评分匹配分析[J]. 中国肿瘤临床, 2023, 50(18): 928-934. DOI: 10.12354/j.issn.1000-8179.2023.20230623
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Fancong Kong, Shaofen Cai, Ling Qi, Dexiang Ji, Min Yu, Yulan Zhou, Shixuan Wang, Fei Li. Prognostic value of PTPN11 mutation in newly diagnosed acute myeloid leukemia: a propensity score matching analysis[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(18): 928-934. DOI: 10.12354/j.issn.1000-8179.2023.20230623
Citation: Fancong Kong, Shaofen Cai, Ling Qi, Dexiang Ji, Min Yu, Yulan Zhou, Shixuan Wang, Fei Li. Prognostic value of PTPN11 mutation in newly diagnosed acute myeloid leukemia: a propensity score matching analysis[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(18): 928-934. DOI: 10.12354/j.issn.1000-8179.2023.20230623
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PTPN11基因突变对初治急性髓系白血病患者的预后影响及倾向性评分匹配分析

Prognostic value of PTPN11 mutation in newly diagnosed acute myeloid leukemia: a propensity score matching analysis

    摘要
  • 摘要:
      目的   分析PTPN11基因突变对初治急性髓系白血病（acute myeloid leukemia，AML）（非M3型）患者预后的影响。
      方法   分析2019年1月至2023年1月在南昌大学第一附属医院确诊且行血液肿瘤相关突变基因全外显子二代测序检测的526例初治AML患者的临床资料，应用倾向性评分匹配（propensity score matching，PSM），根据性别、年龄和ELN 2017危险度分层等因素进行1∶1匹配，比较PTPN11基因突变及未突变患者的临床特征、疗效及预后等方面的差异。
      结果   526例AML患者中，51例（9.7%）患者检测到PTPN11基因突变，包括72种突变类型，均为错义突变。PTPN11突变常与NRAS、DNMT3A、FLT3、NPM1、KRAS等基因伴随出现。PSM后PTPN11突变型（PTPN11 mutation，PTPN11mut）与PTPN11野生型（PTPN11 wild-type，PTPN11wt）患者在完全缓解（complete remission，CR）率（70.8% vs. 56.3%，P=0.138）和总反应率（overall response rate，ORR）（77.1% vs. 66.7%，P=0.256）方面均无显著性差异。PTPN11mut患者中位无复发生存（median relapse-free survival，mRFS）时间为19个月，明显短于PTPN11wt患者未达到（not reached，N/A），（P=0.02），而二者中位总生存（median overall survival，mOS）时间（21.3个月vs. 31.4个月，P=0.416），差异无统计学意义。13例接受异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation，allo-HSCT）的PTPN11mut患者，mOS（N/A vs. 11个月，P=0.001）和mRFS（N/A vs. 5.7个月，P=0.018）均较未接受移植患者明显延长。多因素Cox回归分析显示未接受allo-HSCT、首次诱导疗效未达CR及复发是影响PTPN11mut患者预后的独立危险因素（均P<0.05）。
      结论   PTPN11基因突变AML患者预后不良，allo-HSCT可以显著改善PTPN11mut患者的预后。

     

    Abstract:
      Objective   To determine the prognostic significance of PTPN11 mutation in patients with newly diagnosed acute myeloid leukemia (AML).
      Methods   A total of 526 patients newly diagnosed with AML (non-M3) were screened for gene mutations by whole-exome next generation sequencing. Then, the clinical characteristics, treatment efficacy, and patient survival rate were collected. Patients with PTPN11 mutation were categorized as the PTPN11mut group. The same number of non-PTPN11mut patients were selected as the control group (PTPN11wt), using 1:1 propensity score matching (PSM) for sex, age, and ELN 2017 risk stratification. The differences in efficacy, overall survival, and median relapse-free survival (mRFS) were compared between PTPN11mut and PTPN11wt groups.
      Results   PTPN11 mutations were detected in 51 (9.7%) of 526 patients newly diagnosed with AML, including 72 mutation types, all of which were missense mutations. NRAS, DNMT3A, FLT3, NPM1, and KRAS were the most frequently co-mutated genes of PTPN11. No significant differences were observed in the complete remission (CR) (70.8% vs. 56.3%, P=0.138) and overall response rates (ORR) (77.1% vs. 66.7%, P=0.256) between PTPN11mut and PTPN11wt groups after propensity score matching analysis. The mRFS time of patients with PTPN11mut was 19 months, significantly lower than that of patients with PTPN11wt (not reached, P=0.02), while the median overall survival (mOS) time (21.3 months vs. 31.4 months, P=0.416) did not differ significantly between the two groups. Thirteen patients in the PTPN11mut group underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Moreover, the mOS (not reached vs. 11 months, P=0.001) and mRFS (not reached vs. 5.7 months, P=0.018) in this group were significantly longer than in those who did not receive allo-HSCT. Multivariate analysis showed that no allo-HSCT, failure to achieve CR at first induction, and relapse were independent and significant risk factors in the prognosis of AML patients with PTPN11 mutation (P<0.05).
      Conclusions   Patients with AML that exhibit PTPN11 mutation have a poor prognosis; allo-HSCT significantly improves the prognosis of these patients.

     

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