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费城染色体阳性急性淋巴细胞白血病的可测量残留病动力学与结局的关系。

Association between measurable residual disease kinetics and outcomes of Philadelphia chromosome-positive acute lymphoblastic leukemia.

机构信息

Division of Hematology/Oncology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan.

Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Japan.

出版信息

Ann Hematol. 2021 Oct;100(10):2479-2486. doi: 10.1007/s00277-021-04587-9. Epub 2021 Jul 11.

Abstract

The prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) has improved dramatically. Although measurable residual disease (MRD) kinetics during pretransplant treatment has been recently reported to correlate with patient outcomes, it is unclear whether prognosis is better if the MRD falls below the detection sensitivity soon after induction therapy. We retrospectively analyzed data of 37 Ph + ALL patients who were treated with autologous or allogeneic stem cell transplantation (auto-SCT, allo-SCT) at our institute from 2003 to 2019. Based on MRD kinetics, patients were divided into three groups: early responders (MRD became negative after induction therapy [n = 10, 27.0%]); late responders (MRD remained positive after induction therapy and became negative just before SCT [n = 12, 32.4%]); and poor responders (MRD was positive until just before SCT [n = 15, 40.5%]). The 5-year disease-free survival (DFS) rates for the three groups were 80.0%, 60.0%, and 29.9%, respectively (P = 0.037). The 5-year overall survival rates were not significantly different. The 5-year relapse rates were 0.0%, 31.7%, and 49.5%, respectively (P = 0.045). Non-relapse mortality (NRM) rates were similar among the three groups. Subgroup analysis for the cases that received posttransplantation tyrosine kinase inhibitor maintenance therapy revealed that DFS was similarly dependent on MRD kinetics (P = 0.022). This study clarified that MRD kinetics was a significant prognosticator for DFS and relapse rate in Ph + ALL.

摘要

费城染色体阳性急性淋巴细胞白血病(Ph+ALL)的预后已显著改善。尽管最近有报道称移植前治疗期间的微小残留病(MRD)动力学与患者的结局相关,但在诱导治疗后不久 MRD 降至检测灵敏度以下时,预后是否更好尚不清楚。我们回顾性分析了 2003 年至 2019 年在我院接受自体或异基因干细胞移植(auto-SCT、allo-SCT)治疗的 37 例 Ph+ALL 患者的数据。根据 MRD 动力学,患者被分为三组:早期应答者(诱导治疗后 MRD 转为阴性[n=10,27.0%]);晚期应答者(诱导治疗后 MRD 仍为阳性,在 SCT 前转为阴性[n=12,32.4%]);和不良应答者(在 SCT 前一直为阳性[n=15,40.5%])。三组患者的 5 年无病生存率(DFS)分别为 80.0%、60.0%和 29.9%(P=0.037)。5 年总生存率无显著差异。5 年复发率分别为 0.0%、31.7%和 49.5%(P=0.045)。三组患者的非复发死亡率(NRM)无显著差异。接受移植后酪氨酸激酶抑制剂维持治疗的病例亚组分析表明,DFS 同样依赖于 MRD 动力学(P=0.022)。本研究表明,MRD 动力学是 Ph+ALL 患者 DFS 和复发率的重要预后因素。

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