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The impact of tyrosine kinase inhibitors on allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
Leukemia Research ( IF 2.7 ) Pub Date : 2021-06-18 , DOI: 10.1016/j.leukres.2021.106647
Yuanfeng Zhang 1 , Sizhou Feng 2
Affiliation  

In the tyrosine kinase inhibitor (TKI) era, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still the most potential approach for cure of adult patients with Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL). TKI plus chemotherapy has strikingly increased response rates and depth of response, and facilitated allo-HSCT, which decreases relapse and improves survival eventually. Meanwhile, for those with older age or comorbidities at diagnosis, TKI in combination with reduced-intensity chemotherapy or chemotherapy-free strategy reduces treatment-related mortality, deferred intensive chemotherapy increases molecular responses and reduced-intensity conditioning (RIC) allo-HSCT improves survival finally. Of note, according to minimal residual disease (MRD) and BCR/ABL1 kinase domain mutation screening, prophylactic or preemptive maintenance therapy with a sensitive TKI decreases relapse further. Regarding transplantation-related mortality and impaired quality of life related to complications of allo-HSCT, autologous-HSCT (auto-HSCT) among those with early and persistent molecular remission and the most potent TKI ponatinib plus intensive chemotherapy has exhibited non-inferior survival to allo-HSCT. Even so, risk-adapted strategy isn’t available now. Lastly, outcomes of relapse after allo-HSCT are dismal due to TKIs exposure, and new therapeutic interventions combined with TKIs shed light on this thorny problem.



中文翻译:

酪氨酸激酶抑制剂对费城染色体阳性急性淋巴细胞白血病成年患者异基因造血干细胞移植的影响

在酪氨酸激酶抑制剂(TKI)时代,异基因造血干细胞移植(allo-HSCT)仍然是治愈费城染色体阳性急性淋巴细胞白血病(Ph +全部)。TKI 加化疗显着提高了反应率和反应深度,并促进了异基因造血干细胞移植,最终减少了复发并提高了生存率。同时,对于年龄较大或诊断时有合并症的患者,TKI 联合低强度化疗或无化疗策略可降低治疗相关死亡率,延迟强化化疗可增加分子反应,而低强度条件反射 (RIC) allo-HSCT 可提高生存率最后。值得注意的是,根据微小残留病 (MRD) 和 BCR/ABL1 激酶域突变筛查,使用敏感 TKI 的预防性或抢先性维持治疗可进一步减少复发。关于同种异体造血干细胞移植并发症相关的移植相关死亡率和生活质量受损,自体造血干细胞移植(auto-HSCT)在那些具有早期和持续分子缓解和最有效的 TKI 普纳替尼加强化化疗的患者中显示出不劣于异基因造血干细胞移植的生存率。即便如此,风险适应策略现在还不可用。最后,由于 TKI 暴露,allo-HSCT 后复发的结果令人沮丧,新的治疗干预措施与 TKI 相结合揭示了这个棘手的问题。

更新日期:2021-06-18
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