[1]陈晨,许娜,江雪杰,等.T315I 基因突变的慢性髓性白血病临床特征及泊那替尼疗效[J].南方医科大学学报,2019,(03):364.[doi:10.12122/j.issn.1673-4254.2019.03.16]
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T315I 基因突变的慢性髓性白血病临床特征及泊那替尼疗效()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2019年03期
页码:
364
栏目:
出版日期:
2019-04-11

文章信息/Info

Title:
Clinical characteristics of chronic myeloid leukemia with T315I mutation and the efficacy of ponatinib
作者:
陈晨许娜江雪杰吴婉儿周璇刘靓黄继贤阴常欣曹睿廖立斌徐丹张宇明刘启发刘晓力
关键词:
慢性髓系白血病BCR-ABLT315I泊那替尼异基因造血干细胞移植
Keywords:
chronic myeloid leukemia BCR-ABL T315I ponatinib hematopoietic stem cell transplantation
DOI:
10.12122/j.issn.1673-4254.2019.03.16
摘要:
目的分析伴T315I突变的慢性髓系白血病(CML)的临床特征及不同治疗方法的疗效。方法回顾性分析19例行BCRABL KD突变检测T315I突变的CML患者的临床资料及不同治疗的预后,通过直接测序分析获得用于RTQ-PCR样品的BCRABL KD突变。用Sanger测序法对BCR-ABL KD突变进行测序。复发标准包括血液学复发、细胞遗传学复发和分子生物学复 发。结果19例CML-T315I患者,初诊时73.7%(14/19例)患者处于慢性期(CP),Sokal评分中高危患者占81.2%(13/16例)。19 例患者初诊后均行酪氨酸激酶抑制剂(TKI)治疗,病程中78.9%(15/19例)患者有附加染色体畸变,52.6%(10/19例)患者存在多 重突变。68.4%(13/19 例)的患者在疾病进展后(加速期/急变期)检测出T315I 突变,从初诊到检测出T315I 突变的中位期为 40 m(5~120 m)。突变后12例行泊那替尼治疗(A组),7例选择传统化疗方案(B组)。A、B两组3年总生存率分别是83.3%和 14.2%(P=0.001)。结论小样本回顾性研究发现对TKI耐药的CML患者易检出T315I 突变,进展期检出率明显高于慢性期。 此类患者往往合并附加染色体和多重基因突变,预后较差,即行异基因造血干细胞移植,复发率仍较高。泊纳替尼长期维持治 疗,可能会改善预后,延长生存期。
Abstract:
Objective To analyze the clinical features of chronic myeloid leukemia (CML) with T315 I mutation (CML-T315I) and compare the effectiveness of different treatments. Methods 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. Results 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 (P<0.001). Conclusions 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.

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更新日期/Last Update: 1900-01-01