Association between measurable residual disease kinetics and outcomes of Philadelphia chromosome-positive acute lymphoblastic leukemia
Association between measurable residual disease kinetics and outcomes of Philadelphia chromosome-positive acute lymphoblastic leukemia
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DOI：
10.1007/s00277-021-04587-9
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发表时间：
2021-07-11
影响因子：
3.5
通讯作者：
Ando, Kiyoshi
中科院分区：
文献类型：
--
作者：
Hara, Ryujiro;Onizuka, Makoto;Ando, Kiyoshi
费城染色体阳性急性淋巴细胞白血病（Ph+ALL）的预后已显着改善。尽管最近有报道称移植前治疗期间的可测量残留病 (MRD) 动力学与患者预后相关，但尚不清楚如果诱导治疗后 MRD 很快降至检测灵敏度以下，预后是否会更好。我们回顾性分析了2003年至2019年在我所接受自体或异体干细胞移植（auto-SCT、allo-SCT）的37例Ph + ALL患者的数据。根据MRD动力学，将患者分为三组：早期反应者（诱导治疗后MRD转阴[n = 10, 27.0%]）；早期反应者（诱导治疗后MRD转阴[n = 10, 27.0%]）；晚期反应者（诱导治疗后 MRD 保持阳性，在 SCT 前转为阴性 [n = 12, 32.4%]）；反应不佳者（直到 SCT 前 MRD 才呈阳性 [n = 15, 40.5%]）。三组的5年无病生存率（DFS）分别为80.0%、60.0%和29.9%（P = 0.037）。 5年总生存率没有显着差异。 5年复发率分别为0.0%、31.7%和49.5%（P = 0.045）。三组之间的非复发死亡率（NRM）相似。对接受移植后酪氨酸激酶抑制剂维持治疗的病例进行的亚组分析显示，DFS 同样依赖于 MRD 动力学（P = 0.022）。这项研究阐明，MRD 动力学是 Ph + ALL 患者 DFS 和复发率的重要预测因素。
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.