[The prognostic significance of minimal residual disease detection after first induction treatment in adult acute lymphoblastic leukemia patients treated with autologous stem cell transplantation]

Zhonghua Xue Ye Xue Za Zhi. 2019 Feb 14;40(2):105-110. doi: 10.3760/cma.j.issn.0253-2727.2019.02.003.
[Article in Chinese]

Abstract

Objective: To investigate the prognostic significance of detection of minimal residual disease after first induction treatment (MRD(1)) in adult acute lymphoblastic leukemia (ALL) patients treated with autologous stem cell transplantation (auto-HSCT). Methods: The clinical data of 87 ALL patients who underwent auto-HSCT during February 2006 to April 2017 with MRD(1) detection data by flow cytometry were analyzed retrospectively. The relationship between MRD(1) and relapse and survival of ALL patients after auto-HSCT was studied. Results: Of 87 patients, 26 (29.9%) were MRD(1) positive. The proportion of high-risk immunophenotype (pro-B, pro-T, pre-T, mature T) was significantly higher in MRD(1)-positive patients than that in MRD(1) negative patients (34.6% vs 14.5%, P=0.038). There was no significant difference between positive and negative MRD(1) patients at age, sex, lineage (T/B), immunophenotype (standard risk/high risk), high white blood cell count (B-ALL>30×10(9)/L or T-ALL>100×10(9)/L), high-risk chromosome/gene ratio, the time from first complete remission to transplantation and pre-treatment regimen. The 5-year overall survival (OS) and leukemia-free survival (LFS) in MRD(1) negative and positive patients were 72.7% vs 47.3% (P=0.004) and 75.7% vs 29.6% (P<0.001), respectively. Multivariate analysis showed that positive MRD(1) was an independent risk factor for OS (HR=3.007, 95% CI 1.256-7.200, P=0.013) , and positive MRD(1) and high-risk immunophenotype were risk factors for LFS (HR=3.986, 95% CI 1.813-8.764, P=0.001; HR=2.981, 95% CI 1.373-6.473, P=0.006) . Conclusions: Auto-HSCT could not reverse the poor prognosis of MRD(1) positive patients. Auto-HSCT treatment is optional for patients with MRD(1) negative and maintaining MRD(1) negative status during intensive therapy.

目的: 探讨成人急性淋巴细胞白血病(ALL)患者首疗程诱导治疗结束时微小残留病(MRD(1))检测对自体造血干细胞移植(auto-HSCT)预后的意义。 方法: 回顾性分析2006年2月1日至2017年4月30日行auto-HSCT的87例有流式细胞术MRD(1)检测结果的ALL患者临床资料,分析MRD(1)与ALL患者auto-HSCT后复发、生存的关系。 结果: 26例(29.9%)ALL患者MRD(1)阳性。高危免疫表型比例在MRD(1)阳性组显著高于MRD(1)阴性组(34.6%对14.5%,P=0.038),初诊时年龄、性别、谱系(T/B)、免疫表型(标危/高危)、高白细胞计数(B-ALL>30×10(9)/L或T-ALL>100×10(9)/L)比例、伴高危染色体/基因比例、第1次完全缓解到移植的时间、预处理方案在MRD(1)阴性组和阳性组中差异均无统计学意义(P值均>0.05)。MRD(1)阴性患者、MRD(1)阳性患者的5年无白血病生存(LFS)率分别为75.7%、29.6%(P<0.001),总生存(OS)率分别为72.7%、47.3%(P=0.004)。多因素分析结果显示MRD(1)阳性是影响患者OS的独立危险因素(HR=3.007,95% CI 1.256~7.200,P=0.013),MRD(1)阳性和高危免疫表型是影响患者LFS的危险因素(HR=3.986,95% CI 1.813~8.764,P=0.001;HR=2.981,95% CI 1.373~6.473,P=0.006)。 结论: auto-HSCT不能逆转MRD(1)阳性患者的不良预后。MRD(1)阴性且在强化治疗中持续保持阴性患者可选择auto-HSCT治疗。.

Keywords: Hematopoietic stem cell transplantation; Leukemia, lymphocyte, acute; Minimal residual disease; Prognosis.

MeSH terms

  • Adult
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Neoplasm, Residual
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  • Prognosis
  • Retrospective Studies
  • Transplantation, Autologous