白消安联合环磷酰胺与全身照射联合环磷酰胺治疗成人急性 B 淋巴细胞白血病的比较：一项开放标签、多中心、III 期临床试验。

Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial.

机构信息

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

Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

J Clin Oncol. 2023 Jan 10;41(2):343-353. doi: 10.1200/JCO.22.00767. Epub 2022 Sep 9.

PURPOSE

It remains controversial whether busulfan-based versus total body irradiation (TBI)-based regimens have comparable outcomes in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (allo-HSCT). We investigated the efficacy and toxicity of busulfan plus cyclophosphamide (BuCy) and TBI plus cyclophosphamide (TBI-Cy) conditioning in allo-HSCT for adult standard-risk B-cell-ALL in first complete remission (CR1).

PATIENTS AND METHODS

We performed an open-label, randomized phase III trial at 13 hospitals in China. Eligible patients (age 14-65 years) had standard-risk ALL in CR1. Patients were randomly assigned (1:1) to BuCy (0.8 mg/kg four times per day on days -7 to -4 and cyclophosphamide 60 mg/kg once daily on days -3 to -2) or TBI-Cy (4.5 Gy TBI on days -5 to -4 and cyclophosphamide 60 mg/kg once daily on days -3 to -2). The primary end point was 2-year overall survival. Analysis was per protocol. This trial is registered with ClinicalTrials.gov (identifier: NCT02670252) and is complete.

RESULTS

Between January 2016 and February 2020, 275 patients were assigned to receive BuCy (273 assessed) and 275 to TBI-Cy (272 assessed). The 2-year overall survival was 76.6% (95% CI, 71.7 to 81.8) and 79.4% (74.7 to 84.4; = .457; difference 2.9%; 95% CI, -4.1 to 9.8; = .022), indicating noninferiority of BuCy. The 2-year relapse was 20.2% (95% CI, 15.6 to 25.1) and 18.4% (14.0 to 23.2; = .616), and the nonrelapse mortality was 11.0% (95% CI, 7.6 to 15.0) and 11.0% (7.7 to 15.1; = .988) in the BuCy and TBI-Cy groups, respectively. There were no differences in regimen-related toxicity, graft-versus-host disease, or late effects between the two groups.

CONCLUSION

The BuCy regimen has noninferior efficiency and safety as TBI-Cy (4.5 Gy × 2) for patients with adult standard-risk B cell-ALL in CR1 undergoing HLA-matched allo-HSCT.

目的

在接受异基因造血干细胞移植（allo-HSCT）的急性淋巴细胞白血病（ALL）患者中，与全身照射（TBI）相比，基于白消安的方案是否具有可比的结局仍存在争议。我们研究了在成人标准风险 B 细胞 ALL 首次完全缓解（CR1）中，白消安联合环磷酰胺（BuCy）与 TBI 联合环磷酰胺（TBI-Cy）预处理在 allo-HSCT 中的疗效和毒性。

患者和方法

我们在中国的 13 家医院进行了一项开放标签、随机 III 期试验。符合条件的患者（年龄 14-65 岁）患有标准风险的 ALL，处于 CR1。患者被随机分配（1:1）接受 BuCy（-7 至-4 日每日 4 次 0.8mg/kg，-3 至-2 日每日 1 次 60mg/kg 环磷酰胺）或 TBI-Cy（-5 至-4 日 4.5GyTBI，-3 至-2 日每日 1 次 60mg/kg 环磷酰胺）。主要终点是 2 年总生存率。分析是基于方案的。该试验在 ClinicalTrials.gov 注册（标识符：NCT02670252），现已完成。

结果

2016 年 1 月至 2020 年 2 月期间，275 名患者被分配接受 BuCy（273 名评估），275 名患者接受 TBI-Cy（272 名评估）。2 年总生存率为 76.6%（95%CI，71.7-81.8）和 79.4%（74.7-84.4；=.457；差异 2.9%；95%CI，-4.1-9.8；=.022），表明 BuCy 无劣效性。2 年复发率为 20.2%（95%CI，15.6-25.1）和 18.4%（14.0-23.2；=.616），BuCy 和 TBI-Cy 组的非复发死亡率分别为 11.0%（95%CI，7.6-15.0）和 11.0%（7.7-15.1；=.988）。两组之间在方案相关毒性、移植物抗宿主病或晚期效应方面没有差异。