Addition of venetoclax to myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in high-risk AML.

IF 4.3 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Annals of medicine Pub Date : 2023-12-01 DOI:10.1080/07853890.2022.2164610

Xing-Yu Cao, Jia-Qi Chen, Hui Wang, Wei Ma, Wei-Wei Liu, Fang-Fang Zhang, Song Xue, Lei Dong, Ting Liu, Xiao-Zhen Zhao, Chan-Chan Liu, Xin Xu, Yang He, Lei Wang, Jian-Ling Wang

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引用次数: 1

Abstract

Background: Venetoclax monotherapy is an effective option for patients with acute myeloid leukemia (AML). Venetoclax has also been used in non-myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk AML with a tolerable toxicity profile. However, the efficacy and safety of a venetoclax-containing myeloablative conditioning (MAC) allo-HSCT regimen for high-risk AML have not been evaluated.

Objective: To evaluate the safety and efficacy of a MAC regimen containing venetoclax for high-risk AML.

Study design: From 25 February 2021 to 4 September 2022, a total of 31 patients with high-risk AML who underwent allo-HSCT and a MAC regimen with venetoclax were analyzed.

Results: At the time of transplantation, 21 patients were in first complete remission (CR1), 4 were in a second complete remission (CR2), and 6 in non-remission (NR). Twenty-four patients (77.4%) were minimal residual disease (MRD)-positive before transplant. The FLT3-ITD gene mutation was present in 51.6% of patients. NUP98 rearrangement, MLL rearrangement or MLL-PTD and DEK::CAN fusion genes were found in 5 (16.1%), 7(22.6%) and 2 (6.5%) patients, respectively. Twenty-nine (93.6%) patients underwent haploidentical allo-HSCT. The median follow-up time was 278 days (range: 52-632 days). The 100-day cumulative incidence of grade 3 to 4 acute graft-versus-host disease (aGVHD) was 16.1% (95%CI, 7.2-36.0%). The 180-day cumulative incidence of moderate to severe chronic graft-versus-host disease (cGVHD) was 7.1% (95%CI, 1.9-26.9%). Cumulative incidence of 100-day cytomegalovirus (CMV) viraemia and 100-day Epstein-Barr virus (EBV) viraemia was 61.6% (95%CI, 46.5-81.4%) and 3.2% (95%CI, 0.4-22.2%), respectively. The 600-day overall survival (OS) and leukemia-free survival (LFS) were 80.9% (95%CI, 63.5-93.6%) and 81.3% (95%CI, 64.2-93.7%), respectively. The 600-day relapse incidence (RI) and non-relapse mortality (NRM) was 6.9% (95%CI, 1.8-26.3%) and 11.7% (95%CI, 3.9-35.0%).

Conclusion: Our study shows that the addition of venetoclax to a MAC allo-HSCT was feasible, safe and effective for high-risk AML patients.

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在高危AML异基因造血干细胞移植的清髓调理方案中添加venetoclax。

背景：Venetoclax单药治疗是治疗急性粒细胞白血病（AML）的有效选择。Venetoclax也被用于非清髓性条件异基因造血干细胞移植（allo-HSCT），用于具有可耐受毒性的高危AML。然而，含有venetoclax的清髓性调理（MAC）allo-HSCT方案治疗高危AML的疗效和安全性尚未得到评估。目的：评估含venetoclax的MAC方案治疗高危AML的安全性和有效性。研究设计：从2021年2月25日至2022年9月4日，共分析了31名接受异基因造血干细胞移植和含venetoclax的MAC治疗的高危AML患者。结果：在移植时，21名患者处于首次完全缓解（CR1），4名患者处于第二次完全缓解（CR2），6名患者处于非缓解（NR）。24名患者（77.4%）在移植前为微小残留病（MRD）阳性。FLT3-ITD基因突变在51.6%的患者中存在。NUP98重排、MLL重排或MLL-PTD和DEK:：CAN融合基因分别在5例（16.1%）、7例（22.6%）和2例（6.5%）患者中发现。29例（93.6%）患者接受了单倍体异基因造血干细胞移植。中位随访时间为278 天（范围：52-632 天）。3至4级急性移植物抗宿主病（aGVHD）的100天累积发病率为16.1%（95%CI，7.2-36.0%）。中度至重度慢性移植物抗逆转录病毒病（cGVHD）180天累积发生率为7.1%（95%CI，1.9-26.9%）。100天巨细胞病毒（CMV）病毒血症和100天EB病毒（EBV）病毒贫血的累积发病率分别为61.6%（95%CI、46.5-81.4%）和3.2%（95%可信区间，0.4-22.2%）。600天总生存率（OS）和无白血病生存率（LFS）分别为80.9%（95%可信区间，63.5-93.6%）和81.3%（95%置信区间，64.2-93.7%）。600天复发发生率（RI）和非复发死亡率（NRM）分别为6.9%（95%CI，1.8-26.3%）和11.7%（95%CI，3.9-35.0%）。

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来源期刊

Annals of medicine 医学-医学：内科

CiteScore

4.90

自引率

0.00%

发文量

292

审稿时长

3 months

期刊介绍： Annals of Medicine is one of the world’s leading general medical review journals, boasting an impact factor of 5.435. It presents high-quality topical review articles, commissioned by the Editors and Editorial Committee, as well as original articles. The journal provides the current opinion on recent developments across the major medical specialties, with a particular focus on internal medicine. The peer-reviewed content of the journal keeps readers updated on the latest advances in the understanding of the pathogenesis of diseases, and in how molecular medicine and genetics can be applied in daily clinical practice.