Haploidentical peripheral blood stem cells combined with bone marrow or unrelated cord blood as grafts for haematological malignancies: an open-label, multicentre, randomised, phase 3 trial.

We aimed to assess whether transplantation of haploidentical peripheral blood stem cells (PBSCs) plus unrelated cord blood would achieve superior disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in this population.

我们的目标是评估半相合外周血干细胞（PBSCs）联合无关脐带血移植是否比半相合PBSCs联合骨髓移植在这一人群中实现更好的无病生存率。

Methods

We did an open-label, randomised, phase 3 trial at seven hospitals in China.

我们在中国的七家医院开展了一项开放标签、随机、III期试验。

Eligible patients (aged 18-65 years) had a diagnosis of haematological malignancy, an Eastern Cooperative Oncology Group performance status of 0-2 and transplant comorbidity index of 0-2, and were receiving their first allogenic haematopoietic stem cell transplant.

符合条件的患者（年龄在18-65岁之间）被诊断为血液恶性肿瘤，东协作肿瘤学组表现状态为0-2，移植合并症指数为0-2，并且正在接受他们的首次异基因造血干细胞移植。

Patients were randomly assigned (1:1) to receive transplantation of haploidentical PBSCs plus bone marrow or haploidentical PBSCs plus unrelated cord blood.

患者被随机分配（1:1）接受半相合外周血干细胞加骨髓移植或半相合外周血干细胞加无关脐带血移植。

The primary endpoint was 1-year disease-free survival. All efficacy and safety endpoints were assessed in the intention-to-treatpopulation.

主要终点是1年无病生存率。所有疗效和安全性终点均在意向治疗人群中评估。

This trial is registered with ClinicalTrials.gov (NCT05290545) and is complete.

该试验已在ClinicalTrials.gov上注册（NCT05290545），且已完成。

Results

Between March 5, 2022, and Jan 2, 2023, 357 participants were screened for eligibility, and 314 were randomly assigned to receive transplantation of haploidentical PBSCs plus unrelated cord blood (n=157) or haploidentical PBSCs plus bone marrow (n=157).

在2022年3月5日至2023年1月2日期间，共有357名参与者接受了资格筛查，其中314名被随机分配接受半相合外周血干细胞（PBSCs）联合无关脐带血（n=157）或半相合外周血干细胞（PBSCs）联合骨髓（n=157）的移植。

Median follow-up was 17·2 months (IQR 10·0-20·8) after random assignment. 1-year disease-free survival was 82·2% (95% CI 75·2-87·3) in the group receiving haploidentical PBSCs plus unrelated cord blood (PBSCs plus unrelated cord blood group) and 65·6% (57·6-72·5) in the group receiving haploidentical PBSCs plus bone marrow ([PBSCs plus bone marrow group] hazard ratio[HR] 0·47, 95% CI 0·30-0·74; p=0·0010).

随机分配后中位随访时间为17.2个月（四分位数间距10.0-20.8）。接受半相合外周血干细胞加无关脐带血（PBSCs加无关脐带血组）的患者1年无病生存率为82.2%（95%置信区间75.2-87.3），而接受半相合外周血干细胞加骨髓（PBSCs加骨髓组）的患者为65.6%（57.6-72.5），两组的危险比（HR）为0.47（95%置信区间0.30-0.74；p=0.0010）。

The most common grade 3-5 adverse events within 100 days of transplantation in participants in the PBSCs plus unrelated cord blood and PBSCs plus bone marrow groups were infections (58 [37%] of 157 vs 77 [49%] of 157, p=0·030), acute graft-versus-host disease (49 [31%] vs 61 [39%]), and gastrointestinal disorders (38 [24%] vs 38 [24%]).

在移植后100天内，PBSCs加无关脐带血组和PBSCs加骨髓组中最常见的3-5级不良事件是感染（157名参与者中有58例[37%]对比157名中有77例[49%]，p=0.030）、急性移植物抗宿主病（分别为49例[31%]对比61例[39%]）和胃肠道疾病（均为38例[24%]）。

Seven (4%) patients in the PBSCs plus unrelated cord blood group and 17 (11%) in the PBSCs plus bone marrow group died of transplantation-related causes within 100 days of transplantation.

在移植后100天内，PBSCs联合无关脐带血组有7名（4%）患者因移植相关原因死亡，而PBSCs联合骨髓组有17名（11%）患者死亡。

Causes of deaths in the PBSCs plus unrelated cord blood group versus the PBSCs plus bone marrow group included infections (four [3%] vs 11 [7%]), acute graft-versus-host disease (one [1%] vs three [2%]), vascular disorders (two [1%] vs one [1%]), cardiac disorders (none vs one [1%]), and respiratory disorders (none vs one [1%]).

与PBSCs联合骨髓组相比，PBSCs联合无关脐带血组的死亡原因包括感染（四名[3%]对11名[7%]）、急性移植物抗宿主病（一名[1%]对三名[2%]）、血管疾病（两名[1%]对一名[1%]）、心脏疾病（无对一名[1%]）和呼吸系统疾病（无对一名[1%]）。

interpretation

Transplantation of haploidentical PBSCs plus unrelated cord blood achieved superior 1-year disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in patients with haematological malignancies, with a more satisfactory safety profile.

在血液恶性肿瘤患者中，半相合外周血干细胞联合无关脐带血移植在1年无病生存率上优于半相合外周血干细胞联合骨髓移植，并且安全性更令人满意。

Our results suggest that combining haploidentical PBSCs with unrelated cord blood, rather than with bone marrow, could be a better treatment option for this population.

我们的结果表明，对于这一人群，将半相合外周血干细胞与无关脐带血结合使用，而不是与骨髓结合，可能是一种更好的治疗选择。

funding

None.

无。