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T315I mutation exerts a dismal prognosis on adult BCR-ABL1-positive acute lymphoblastic leukemia, and salvage therapy with ponatinib or CAR-T cell and bridging to allogeneic hematopoietic stem cell transplantation can improve clinical outcomes.
Annals of Hematology ( IF 3.5 ) Pub Date : 2020-02-27 , DOI: 10.1007/s00277-020-03949-z
Shi Ting 1, 2 , Xie Mixue 1 , Zhu Lixia 1 , Li Xueying 1 , Xie Wanzhuo 1 , Ye Xiujin 1
Affiliation  

A single-center retrospective was performed with consecutive de novo BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients who received TKI-containing therapy between January 2010 and December 2018 to review the incidence, treatment, and outcome of the T315I mutation. A total of 38 (18%) patients harbored the T315I mutation in this period. According to the type of salvage therapy, patients were divided into subgroups of hematopoietic stem cell transplantation (HSCT) recipients (n = 9) and HSCT nonrecipients (n = 29). In the latter subgroup, there were 7 patients who newly acquired the T315I mutation after HSCT, and the median time was 10.8 months. In addition to these 7 cases, 5 out of 22 patients were managed with chimeric antigen receptor (CAR) T cells and ponatinib. There were 4 patients in the HSCT recipient subgroup who were treated with CAR-T cells or ponatinib before HSCT. The complete molecular remission (CMR) and recurrence rate of HSCT recipients were both 67%, and the median recurrence time was 3.6 months. A better overall survival (OS) was observed in the HSCT recipient subgroup than in the HSCT nonrecipient subgroup (median of 12.3 months vs 3.3 months, respectively; p = 0.004). Compared with patients who were not bridging to HSCT, the patients who were treated with CAR-T cells and/or ponatinib and bridged to HSCT tended to have a better OS (median of 3.3 months vs 13.3, respectively; p = 0.09). In conclusion, the outcomes in ALL patients with the T315I BCR-ABL1 mutation were poor. A better OS can be achieved through ponatinib, CAR-T cells, and bridging to HSCT, but it also has a higher risk of recurrence.

中文翻译:

T315I突变对成人BCR-ABL1阳性急性淋巴细胞白血病预后不佳,使用庞他替尼或CAR-T细胞挽救疗法并桥接同种异体造血干细胞移植可以改善临床效果。

对2010年1月至2018年12月期间接受含TKI治疗的连续从头BCR-ABL1阳性急性淋巴细胞白血病(ALL)患者进行单中心回顾,以回顾T315I突变的发生率,治疗和结局。在此期间,共有38位患者(18%)携带T315I突变。根据挽救疗法的类型,将患者分为造血干细胞移植(HSCT)受者(n = 9)和非接受HSCT的亚组(n = 29)。在后一个亚组中,有7例在HSCT后新获得T315I突变,平均时间为10.8个月。除这7例外,22例患者中有5例接受了嵌合抗原受体(CAR)T细胞和ponatinib的治疗。HSCT受体亚组中有4例患者在HSCT之前接受过CAR-T细胞或ponatinib的治疗。HSCT受体的完全分子缓解(CMR)和复发率均为67%,中位复发时间为3.6个月。在HSCT接受者亚组中观察到的总生存期(OS)比在HSCT非接受者亚组中更好(中位数分别为12.3个月和3.3个月; p = 0.004)。与未桥接HSCT的患者相比,接受CAR-T细胞和/或ponatinib治疗并桥接至HSCT的患者的OS趋向于更好(中位数分别为3.3个月和13.3; p = 0.09)。总之,所有患有T315I BCR-ABL1突变的患者的预后都很差。通过ponatinib,CAR-T细胞并桥接至HSCT,可以获得更好的OS,
更新日期:2020-02-27
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