Salvage therapy containing sorafenib and donor lymphocyte infusion is associated with improved outcomes for FLT3 wild-type acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation.

IF 11.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomarker Research Pub Date : 2025-08-20 DOI:10.1186/s40364-025-00816-9

Zhonghui Jiang, Ya Zhou, Yuxin Bai, Fang Dai, Menglin Fan, Tian Zhang, Danian Nie, Yunxin Zeng, Yirong Jiang, Ping Zhu, Zhiping Fan, Na Xu, Fen Huang, Ren Lin, Min Dai, Xiaojun Xu, Zhangkun Li, Hua Jin, Jing Sun, Qifa Liu, Li Xuan

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引用次数: 0

Abstract

Background: There is no established standard treatment for acute myeloid leukemia (AML) patients with FLT3 wild-type relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Multi-kinase inhibitor sorafenib has been widely explored in the treatment of AML patients with FLT3 internal tandem duplication (FLT3-ITD) mutations. Some studies have revealed that the addition of sorafenib to standard chemotherapy could improve outcomes in newly diagnosed AML regardless of FLT3 status. However, the application of sorafenib in FLT3 wild-type AML patients experiencing relapse after allo-HSCT remains minimally investigated.

Methods: We retrospectively compared the effects of conventional treatment combined with or without sorafenib on the outcomes of these patients. The study mainly focused on the treatment response of salvage therapy and survival.

Results: Sixty-two AML patients with FLT3 wild-type who relapsed after allo-HSCT were enrolled in this study, including 38 with sorafenib and 24 without sorafenib. Fifty patients received 68 doses of donor lymphocyte infusion (DLI). The rate of composite complete remission was 65.8% in the sorafenib group, compared with 29.2% in the non-sorafenib group (P = 0.005). With a median follow-up of 13.2 months (IQR, 3.2-43.5) after relapse, the 2-year overall survival (OS) was 47.4% (95%CI, 33.9%-66.2%) and 16.7% (6.8%-40.8%) in the sorafenib and non-sorafenib groups (P = 0.006). The 2-year event-free survival (EFS) was 44.7% (31.4%-63.7%) and 16.7% (6.8%-40.8%) in the two groups (P = 0.012). Multivariable analysis revealed that salvage therapy including sorafenib was the protective factor for longer OS and EFS (HR = 0.395, 95% CI: 0.209-0.746, P = 0.004; HR = 0.406, 95% CI: 0.218-0.754, P = 0.004). The incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were similar between the two groups (P = 0.806, P = 0.908).

Conclusion: Our results suggest that salvage therapy including sorafenib and DLI is associated with improved outcomes for AML patients with FLT3 wild-type relapsing after allo-HSCT.

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含有索拉非尼和供体淋巴细胞输注的补救性治疗与同种异体造血干细胞移植后FLT3野生型急性髓性白血病复发的改善结果相关。

背景：对于同种异体造血干细胞移植（alloo - hsct）后FLT3野生型复发的急性髓系白血病（AML）患者，尚无既定的标准治疗方法。多激酶抑制剂索拉非尼在FLT3内串联重复（FLT3- itd）突变AML患者的治疗中被广泛探索。一些研究表明，无论FLT3状态如何，在标准化疗中加入索拉非尼都可以改善新诊断的AML的预后。然而，索拉非尼在同种异体造血干细胞移植后复发的FLT3野生型AML患者中的应用研究仍然很少。方法：我们回顾性比较常规治疗联合或不联合索拉非尼对这些患者预后的影响。本研究主要集中在挽救治疗的治疗反应和生存。结果：本研究纳入了62例同种异体造血干细胞移植后复发的FLT3野生型AML患者，其中38例使用索拉非尼，24例未使用索拉非尼。50例患者接受68次供体淋巴细胞输注（DLI）。索拉非尼组复合完全缓解率为65.8%，非索拉非尼组为29.2% （P = 0.005）。复发后中位随访13.2个月（IQR, 3.2 ~ 43.5），索拉非尼组和非索拉非尼组2年总生存率（OS）分别为47.4% （95%CI, 33.9% ~ 66.2%）和16.7% (6.8% ~ 40.8%)（P = 0.006）。两组患者的2年无事件生存率（EFS）分别为44.7%（31.4% ~ 63.7%）和16.7% (6.8% ~ 40.8%)（P = 0.012）。多变量分析显示，包括索拉非尼在内的挽救性治疗是延长OS和EFS的保护因素（HR = 0.395, 95% CI: 0.209-0.746, P = 0.004; HR = 0.406, 95% CI: 0.218-0.754, P = 0.004）。两组间急性移植物抗宿主病（GVHD）和慢性移植物抗宿主病（GVHD）发生率相似（P = 0.806, P = 0.908）。结论：我们的研究结果表明，包括索拉非尼和DLI在内的挽救性治疗与同种异体造血干细胞移植后FLT3野生型复发的AML患者的预后改善有关。

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来源期刊

Biomarker Research Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

15.80

自引率

1.80%

发文量

审稿时长

10 weeks

期刊介绍： Biomarker Research, an open-access, peer-reviewed journal, covers all aspects of biomarker investigation. It seeks to publish original discoveries, novel concepts, commentaries, and reviews across various biomedical disciplines. The field of biomarker research has progressed significantly with the rise of personalized medicine and individual health. Biomarkers play a crucial role in drug discovery and development, as well as in disease diagnosis, treatment, prognosis, and prevention, particularly in the genome era.