[The effect of TP53 mutations on the clinical outcomes of Ph-negative B-acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation]

Zhonghua Xue Ye Xue Za Zhi. 2020 Nov 14;41(11):908-914. doi: 10.3760/cma.j.issn.0253-2727.2020.11.005.
[Article in Chinese]

Abstract

Objective: To evaluate the association of TP53 mutations with the clinical outcomes of Ph-negative B-ALL following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Total 300 patients with Ph-negative B-ALL who underwent allo-HSCT at the Hebei Yanda Ludaopei Hospital from May 2012 to May 2017 were retrospectively analyzed; their clinical characteristics, TP53 gene mutation type, and association between TP53 mutations and transplantation outcomes, including leukemia-free survival (LFS) , overall survival (OS) , non-relapse mortality (NRM) , relapse, and GVHD, were evaluated. Results: Total 23 patients had TP53 mutations; all the TP53 mutations affected P53'DNA-binding domain. The 5-year-LFS, OS, and RI were 34.8% and 62.3% (P=0.001) , 41.9% and 65.1% (P=0.020) , and 47.8% and 14.8% (P=0.000) , respectively, for TP53 mutations and wild-type TP53 patients. However, there were no significant differences in NRM and GVHD. Multivariate analysis showed that TP53 mutations remained adverse prognostic factors for LFS, OS, and RI after allo-HSCT. Conclusion: Some patients with TP53 mutations can achieve long-term survival with allo-HSCT. TP53 mutations are adverse prognostic factors for Ph-negative B-ALL patients who undergo allo-HSCT.

目的: 探讨TP53基因突变对Ph阴性急性B淋巴细胞白血病(B-ALL)异基因造血干细胞移植(allo-HSCT)疗效的影响。 方法: 回顾性研究2012年5月至2017年5月在河北燕达陆道培医院行allo-HSCT的300例Ph阴性B-ALL患者的临床特点和TP53基因突变发生情况,分析TP53基因突变对移植后无白血病生存(LFS)、总生存(OS)、非复发相关死亡(NRM)、累积复发率(RI)和移植物抗宿主病(GVHD)发生的影响。 结果: 共23例患者检出TP53基因突变,突变位点均位于DNA结合区。TP53基因突变组和非突变组5年LFS率分别为34.8%和62.3%(P=0.001),5年OS率分别为41.9%和65.1%(P=0.020),5年RI分别为47.8%和14.8%(P=0.000),而两组间在GVHD和NRM上差异无统计学意义(P>0.05)。多因素分析显示,TP53基因突变仍然是影响移植后OS、LFS和RI的不良因素。 结论: allo-HSCT可以使部分具有TP53基因突变的Ph阴性B-ALL患者获得长期生存。TP53基因突变是影响Ph阴性B-ALL患者allo-HSCT预后的独立危险因素。.

Keywords: Allogeneic hematopoietic stem cell transplantation; Leukemia, B lymphoblastic, acute; TP53 gene.

MeSH terms

  • Acute Disease
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Mutation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Prognosis
  • Retrospective Studies
  • Transplantation, Homologous
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53