Chen Chen, Xu Na, Jiang Xuejie, Wu Waner, Zhou Xuan, Liu Liang, Huang Jixian, Yin Changxin, Cao Rui, Liao Libin, Xu Dan, Zhang Yuming, Liu Qifa, Liu Xiaoli
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Department of Hematology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2019 Mar 30;39(3):364-368. doi: 10.12122/j.issn.1673-4254.2019.03.16.
To analyze the clinical features of chronic myeloid leukemia (CML) with T315 I mutation (CML-T315I) and compare the effectiveness of different treatments.
We retrospectively analyzed the clinical data and outcomes of 19 patients with CML-T315I receiving different treatments. The T315 I mutations in these patients were detected by examination of BCR-ABL kinase domain (KD) mutation by RTQ-PCR and Sanger sequencing. The relapse following the treatments, defined as hematological, cytogenetic and molecular biological recurrences, were analyzed in these patients.
Of the 19 patients with CML-T315I, 14 (73.7%) were in CML-CP stage at the initial diagnosis, and 13 (81.2%) were high-risk patients based on the Sokal scores. All the 19 patients were treated with TKI after the initial diagnosis, and during the treatment, 15 (78.9%) patients were found to have additional chromosomal aberrations, and 10 (52.6%) had multiple mutations; 13 (68.4%) of the patients experienced disease progression (accelerated phase/blast crisis) before the detection of T315I mutation, with a median time of 40 months (5-120 months) from the initial diagnosis to the mutation detection. After detection of the mutation, 12 patients were treated with ponatinib and 7 were managed with the conventional chemotherapy regimen, and their overall survival rates at 3 years were 83.3% and 14.2%, respectively ( < 0.001).
CML patients resistant to TKI are more likely to have T315I mutations, whose detection rate is significantly higher in the progressive phase than in the chronic phase. These patients often have additional chromosomal aberrations and multiple gene mutations with poor prognoses and a high recurrence rate even after hematopoietic stem cell transplantation. Long-term maintenance therapy with ponatinib may improve the prognosis and prolong the survival time of the patients.
分析T315I突变的慢性髓性白血病（CML-T315I）的临床特征，并比较不同治疗方法的疗效。
回顾性分析19例接受不同治疗的CML-T315I患者的临床资料和治疗结果。通过实时定量聚合酶链反应（RTQ-PCR）和桑格测序检测这些患者的BCR-ABL激酶结构域（KD）突变，以确定T315I突变情况。分析这些患者治疗后的复发情况，复发定义为血液学、细胞遗传学和分子生物学复发。
19例CML-T315I患者中，14例（73.7%）初诊时处于慢性期（CML-CP），根据索卡尔评分，13例（81.2%）为高危患者。所有19例患者初诊后均接受酪氨酸激酶抑制剂（TKI）治疗，治疗期间，15例（78.9%）患者发现有额外的染色体异常，10例（52.6%）有多种突变；13例（68.4%）患者在检测到T315I突变前经历疾病进展（加速期/急变期），从初诊到突变检测的中位时间为40个月（5 - 120个月）。检测到突变后，12例患者接受波纳替尼治疗，7例采用传统化疗方案，其3年总生存率分别为83.3%和14.2%（P<0.001）。
对TKI耐药的CML患者更易发生T315I突变，其在进展期的检出率明显高于慢性期。这些患者常伴有额外的染色体异常和多种基因突变，预后较差，即使造血干细胞移植后复发率也很高。波纳替尼长期维持治疗可能改善患者预后并延长生存时间。
