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费城染色体阳性急性淋巴细胞白血病患者接受异基因造血干细胞移植的真实世界结局——单中心经验

Real world outcomes in patients with Philadelphia chromosome positive acute lymphoblastic leukemia undergoing allogeneic stem cell transplantation-A single institution experience.

作者信息

Takiar Radhika, Foucar Charles E, Perissinotti Anthony J, Marini Bernard L, Benitez-Colon Lydia, Burke Patrick W, Bixby Dale L

机构信息

Division of Hematology and Medical Oncology, Department of Internal Medicine, Michigan Medicine, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48197, USA.

Department of Pharmacy Services and Clinical Pharmacy, Michigan Medicine, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48197, USA.

出版信息

Leuk Res Rep. 2022 Oct 7;18:100352. doi: 10.1016/j.lrr.2022.100352. eCollection 2022.

Abstract

Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) has been associated with a worse prognosis compared to Ph negative ALL. Tyrosine kinase inhibitor (TKI) therapy has led to an improvement in response rates and survival, thus becoming a critical component of therapy. We performed a retrospective cohort study of Ph+ ALL patients treated at the University of Michigan who received TKI therapy pre- and post-allogeneic hematopoietic stem cell transplant (HSCT) from April 2007 to November 2019. The study included 40 patients with Ph+ ALL (47.5% female) with a median age of 54 (24-69) years. Median event-free survival (EFS) was not reached, with a 5-year EFS of 61%. Median overall survival (OS) was not reached, with a 5-year OS of 71%. There was no difference in 2-year EFS or OS for patients on pre-transplant imatinib or dasatinib (p = 0.16, 0.09, respectively), though definitive conclusions are challenging as post-transplant TKI therapy was variable. The incidence of any grade acute graft-versus-host disease (GVHD) was 62.5% (25/40) and any grade chronic GVHD was 77.5% (31/40). Complete molecular remission (CMR) was achieved in 57.5% of patients pre-transplant with no significant difference when stratified by induction TKI (p = 1). Achievement of CMR pre-HSCT showed a trend towards improved 2-year EFS (p=0.0198) but did not significantly change 2-year OS (p = 1). Patients receiving 1 and 2 generation TKIs pre- and post-HSCT seem to have favorable outcomes, although type of TKI (pre-HSCT) did not significantly impact EFS or OS. In addition, attaining a CMR pre-transplant improved EFS, but did not change OS.

摘要

与费城染色体阴性的急性淋巴细胞白血病(ALL)相比,费城染色体阳性(Ph+)的ALL患者预后较差。酪氨酸激酶抑制剂(TKI)治疗提高了缓解率和生存率,因此成为治疗的关键组成部分。我们对2007年4月至2019年11月在密歇根大学接受TKI治疗的Ph+ ALL患者进行了一项回顾性队列研究,这些患者在异基因造血干细胞移植(HSCT)前后均接受了TKI治疗。该研究纳入了40例Ph+ ALL患者(47.5%为女性),中位年龄为54岁(24 - 69岁)。未达到中位无事件生存期(EFS),5年EFS为61%。未达到中位总生存期(OS),5年OS为71%。移植前使用伊马替尼或达沙替尼的患者在2年EFS或OS方面无差异(p分别为0.16和0.09),尽管由于移植后TKI治疗存在差异,难以得出明确结论。任何级别的急性移植物抗宿主病(GVHD)发生率为62.5%(25/40),任何级别的慢性GVHD发生率为77.5%(31/40)。57.5%的患者在移植前实现了完全分子缓解(CMR),按诱导TKI分层时无显著差异(p = 1)。HSCT前实现CMR显示出2年EFS改善的趋势(p = 0.0198),但未显著改变2年OS(p = 1)。HSCT前后接受第一代和第二代TKI治疗的患者似乎预后良好,尽管移植前TKI类型对EFS或OS没有显著影响。此外,移植前达到CMR可改善EFS,但未改变OS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f67/9557030/81842f3e9cb1/gr1.jpg

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