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含地西他滨的强化预处理与标准清髓性预处理用于KMT2A重排白血病成年患者的疗效比较:一项多中心回顾性研究

Intensified conditioning containing decitabine versus standard myeloablative conditioning for adult patients with KMT2A-rearranged leukemia: a multicenter retrospective study.

作者信息

Hu Zhongli, Feng Zinan, Liu Shiqi, He Hai, Dong Ying, Fan Zhiping, Li Yiqing, Huang Fen, Xu Na, Liu Can, Zeng Yunxin, Zhu Ping, Lin Ren, Jin Hua, Zhang Xiong, Sun Ruijuan, Liu Qifa, Xuan Li

机构信息

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Clinical Medical Research Center of Hematology Diseases of Guangdong Province, Guangzhou, China.

出版信息

BMC Med. 2024 Dec 31;22(1):605. doi: 10.1186/s12916-024-03830-0.

Abstract

BACKGROUND

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended for patients with KMT2A-rearranged (KMT2A-r) leukemia whereas relapse remains high. We aimed to determine whether intensified conditioning containing decitabine (Dec) could reduce relapse compared with standard myeloablative conditioning in adult patients with KMT2A-r leukemia.

METHODS

We performed a multicenter retrospective study at seven institutions in China. Eligible patients were aged 14 years or older at transplantation, had a diagnosis of KMT2A-r leukemia, and underwent the first allo-HSCT. Standard myeloablative conditioning regimens (standard group) included BuCy (busulfan 3.2 mg/kg/day on days -7 to -4; cyclophosphamide 60 mg/kg/day on days -3 to -2) and TBI-Cy (total body irradiation 4.5 Gy/day on days -5 to -4; Cy 60 mg/kg/day on days -3 to -2). Intensified conditioning regimens containing Dec (intensified group) consisted of Dec-BuCy (Dec 20 mg/m/day on days -14 to -10; the same dose of BuCy) and Dec-TBI-Cy (Dec 20 mg/m/day on days -10 to -6; the same dose of TBI-Cy).

RESULTS

Between April 2009 and December 2019, 218 patients were included in this study, of whom 105 were in the intensified group and 113 were in the standard group. The 3-year cumulative incidence of relapse was 17.6% and 34.5%, overall survival was 71.3% and 61.0%, disease-free survival was 70.1% and 56.0%, and non-relapse mortality was 12.3% and 9.5% in the intensified and standard groups, respectively (P = 0.001; P = 0.034; P = 0.005; P = 0.629). Subgroup analysis showed that the relapse rate of intensified conditioning was lower than that of standard conditioning in multiple subgroups, including different leukemia types, disease status at transplantation, high-risk cytogenetics and Bu-based regimens. There was no difference in regimen-related toxicity, engraftment, or graft-versus-host disease between the intensified and standard groups.

CONCLUSIONS

These results suggest that intensified conditioning containing Dec might be a better strategy than standard myeloablative conditioning for adult patients with KMT2A-r leukemia undergoing allo-HSCT.

摘要

背景

对于KMT2A重排(KMT2A-r)白血病患者,推荐进行异基因造血干细胞移植(allo-HSCT),但其复发率仍然很高。我们旨在确定与标准清髓性预处理相比,含地西他滨(Dec)的强化预处理能否降低成年KMT2A-r白血病患者的复发率。

方法

我们在中国的7家机构进行了一项多中心回顾性研究。符合条件的患者在移植时年龄为14岁或以上,诊断为KMT2A-r白血病,并接受首次allo-HSCT。标准清髓性预处理方案(标准组)包括BuCy(白消安3.2mg/kg/天,第-7至-4天;环磷酰胺60mg/kg/天,第-3至-2天)和TBI-Cy(全身照射4.5Gy/天,第-5至-4天;环磷酰胺60mg/kg/天,第-3至-2天)。含Dec的强化预处理方案(强化组)包括Dec-BuCy(地西他滨20mg/m²/天,第-14至-10天;相同剂量的BuCy)和Dec-TBI-Cy(地西他滨20mg/m²/天,第-10至-6天;相同剂量的TBI-Cy)。

结果

2009年4月至日2019年12月,本研究共纳入218例患者,其中强化组105例,标准组113例。强化组和标准组的3年累积复发率分别为17.6%和34.5%,总生存率分别为71.3%和61.0%,无病生存率分别为70.1%和56.0%,非复发死亡率分别为12.3%和9.5%(P = 0.001;P = 0.034;P = 0.005;P = 0.629)。亚组分析显示,在多个亚组中,包括不同白血病类型、移植时疾病状态、高危细胞遗传学和基于白消安的方案,强化预处理的复发率低于标准预处理。强化组和标准组在方案相关毒性、植入或移植物抗宿主病方面无差异。

结论

这些结果表明,对于接受allo-HSCT的成年KMT2A-r白血病患者,含Dec的强化预处理可能是比标准清髓性预处理更好地策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11687046/88fc9b648176/12916_2024_3830_Fig1_HTML.jpg

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