Background

The introduction of donors other than HLA-matched siblings has been a pivotal change in stem cell transplantation. We aimed to assess the evolution of outcomes within donor groups over time and explore whether donor–recipient HLA disparity might be advantageous in patients with aggressive disease.

Methods

In this retrospective, multicentre study, we assessed the outcomes for adult patients (≥18 years) with haematological malignancies who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) between Jan 3, 2001, and Dec 31, 2015, and were reported to the European Society for Blood and Marrow Transplantation. The donor types studied were matched sibling, matched unrelated, mismatched unrelated, haploidentical, and cord blood donors. Unrelated non-cord-blood donors and recipients were typed at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRB1. We evaluated trends in overall survival, non-relapse mortality, relapse incidence, progression-free survival, acute and chronic graft-versus-host disease (GVHD), and GVHD-free and relapse-free survival following transplantation from various donor types (matched sibling, matched unrelated, mismatched unrelated, haploidentical, and umbilical cord blood), and compared transplantation outcomes across three epochs (epoch 1: 2001–05; epoch 2: 2006–10; and epoch 3: 2011–15). We used Kaplan-Meier estimators for survival probabilities and cumulative incidence functions accounting for competing risks for probabilities of GHVD, relapse, and non-relapse mortality, using multiple imputations by chained equations to deal with missing data. In epoch 3, we directly compared outcomes by donor group, stratified by a novel three-level disease-risk scheme.

Findings

We included 106 188 patients in our analysis. The median follow-up was 4·1 years (IQR 1·7–7·7). Overall survival at 3 years increased with all donor groups between epochs 2 and 3 (matched sibling: 54·0% [95% CI 53·1–54·8] to 54·6% [53·6–55·6]; matched unrelated: 49·1% [48·0–50·2] to 51·6% [50·7–52·6]; mismatched unrelated: 37·4% [35·7–39·2] to 41·3% [39·5–43·1]; haploidentical: 34·5% [31·4–37·9] to 44·2% [42·1–46·3]; and cord blood 36·3% [33·9–39] to 43·7% [40·8–46·8]). Improvement in overall survival seems to be driven by a reduction in non-relapse mortality, except in cord blood HSCT recipients, who had a lower relapse incidence. Comparing donor groups across disease-risk strata using the novel disease-risk scheme, overall survival among recipients of matched sibling transplantations remained better than other donor groups except in high-risk disease, where overall survival with matched unrelated transplantations was not different.

Interpretation

Overall survival following allogeneic stem cell transplantation is improving with substantial progress among recipients of haploidentical and cord blood HSCT. Nonetheless, the traditional donor hierarchy of matched sibling donors followed by matched unrelated donors and then other donors holds. Our findings warrant further investigation and could inform decision making and the development of donor-selection algorithms.

Funding

The Varda and Boaz Dotan Research Center in Haemato-Oncology, Tel Aviv University, and the Shalvi Foundation for Research.

中文翻译：

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HLA匹配和替代供体的同种异体造血干细胞移植的结果：欧洲血液和骨髓移植学会注册表回顾性分析

背景

除HLA匹配的同胞外，其他捐赠者的引入一直是干细胞移植中的关键变化。我们旨在评估供体组随时间推移的结局演变，并探讨供体与受体之间的HLA差异是否可能对患有侵袭性疾病的患者有利。

方法

在这项回顾性，多中心研究中，我们评估了2001年1月3日至2015年12月间首次接受异基因造血干细胞移植（HSCT）的血液系统恶性肿瘤成年患者（≥18岁）的结局，并报告欧洲血液和骨髓移植学会。研究的供体类型为同胞匹配，不相关，不匹配，单倍体和脐带血供体。在HLA-A，HLA-B，HLA-C和HLA-DRB1等位基因水平上对无关的非脐带血供体和受体进行分型。我们评估了从各种供体类型移植后的总体生存率，非复发死亡率，复发率，无进展生存率，急性和慢性移植物抗宿主病（GVHD）以及无GVHD和无复发生存率的趋势（相匹配同胞，匹配的不相关，错配的不相关，单倍体和脐带血），并比较了三个时期（时期1：2001-05；时期2：2006-10；以及时期3：2011-15）的移植结果。我们使用Kaplan-Meier估计量来求出生存概率，并使用累积发生率函数来计算GHVD概率，复发和非复发死亡率的竞争风险，并通过链式方程式多次插补来处理缺失数据。在第3阶段，我们直接比较了按新的三级疾病风险计划分层的捐赠者组的结局。

发现

我们的分析纳入106188名患者。中位随访时间为4·1年（IQR 1·7-7·7）。在第2和第3阶段之间，所有供体组的3年总生存期均增加（同胞兄弟姐妹：54·0％[95％CI 53·1-54·8]增至54·6％[53·6-55·6]；匹配不相关：49·1％[48·0–50·2]到51·6％[50·7–52·6]；不匹配不相关：37·4％[35·7–39·2]到41· 3％[39·5–43·1]；单倍型：34·5％[31·4–37·9]至44·2％[42·1–46·3]；脐带血36·3％[ 33·9–39]到43·7％[40·8–46·8]）。总生存率的提高似乎是由非复发死亡率的降低所驱动的，除了脐带血HSCT接受者以外，复发率较低。使用新型疾病风险方案比较疾病风险阶层中的捐助者群体，

解释

同种异体和脐带血HSCT受体的接受者在同种异体干细胞移植后的总体存活率不断提高。但是，传统的同级兄弟捐助者的捐助者等级依次是不相关的捐助者，然后是其他捐助者。我们的发现值得进一步研究，并且可以为决策和捐助者选择算法的发展提供参考。

资金

特拉维夫大学血液肿瘤学的Varda和Boaz Dotan研究中心，以及Shalvi研究基金会。