Detection of T315I using digital polymerase chain reaction in allogeneic transplant recipients with Ph-positive acute lymphoblastic anemia in the dasatinib era
Detection of T315I using digital polymerase chain reaction in allogeneic transplant recipients with Ph-positive acute lymphoblastic anemia in the dasatinib era
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DOI：
10.1016/j.exphem.2020.01.001
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发表时间：
2020-01-01
影响因子：
2.6
通讯作者：
Kanda, Yoshinobu
中科院分区：
文献类型：
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作者：
Akahoshi, Yu;Nakasone, Hideki;Kanda, Yoshinobu
达沙替尼是一种有效的酪氨酸激酶抑制剂（TKI），目前用于费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）的一线治疗。然而，T315I突变的出现已被发现是含达沙替尼治疗后失败的主要原因。我们使用数字聚合酶链反应（PCR）技术评估了特定时间点携带T315I突变的小克隆的预后价值，该技术比直接测序更敏感。该研究纳入了25例连续的Ph+ ALL成年患者，他们在我们中心接受了基于达沙替尼的化疗后进行了异体造血干细胞移植（HSCT）。在6例造血干细胞移植后血液学复发的患者中，4例复发时携带T315I突变。然而，在诊断或HSCT中检测到携带T315I的小亚克隆与复发风险增加无关。相比之下，所有HSCT后分子复发时T315I突变的患者（n = 4）最终血液学复发，10例HSCT后分子复发时没有T315I突变的患者中只有2例复发。总之，在HSCT后分子复发时检测到T315I突变的小克隆，而不是在HSCT前，可以支持早期临床决定改变治疗方法。(C) 2020 ISEH -血液与干细胞学会。Elsevier Inc.出版。版权所有。
Dasatinib, a potent tyrosine kinase inhibitor (TKI), is currently used as first-line treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, emergence of the T315I mutation has been found to be a main cause of failure after dasatinib-containing treatments. We assessed the prognostic value of small clones with the T315I mutation at specific time points using the novel technology digital polymerase chain reaction (PCR), which is more sensitive than direct sequencing. This study included 25 consecutive adult patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) following dasatinib-based chemotherapy at our center. Among six patients who experienced hematologic relapse after HSCT, four harbored the T315I mutation at relapse. However, the detection of small subclones with T315I at either diagnosis or HSCT was not associated with an increased risk of relapse. In contrast, all patients with the T315I mutation at molecular relapse after HSCT (n = 4) eventually had a hematologic relapse, and only two of the 10 patients without the T315I mutation at molecular relapse after HSCT relapsed. In conclusion, the detection of small clones with the T315I mutation at molecular relapse after HSCT, but not before HSCT, could support an early clinical decision to change treatments. (C) 2020 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.