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异基因造血干细胞移植后环磷酰胺预防移植物抗宿主病:9/10 或 10/10 HLA 匹配的无关供者用于治疗急性白血病。

Post-transplantation cyclophosphamide GvHD prophylaxis after hematopoietic stem cell transplantation from 9/10 or 10/10 HLA-matched unrelated donors for acute leukemia.

机构信息

Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.

Hôpital Saint-Antoine, Paris University UPMC, INSERM U938, Paris, France.

出版信息

Leukemia. 2021 Feb;35(2):585-594. doi: 10.1038/s41375-020-0863-4. Epub 2020 May 14.

DOI:10.1038/s41375-020-0863-4
PMID:32409688
Abstract

HLA-matching largely contributes to unrelated donor hematopoietic cell transplantation (UD-HCT) success but, due to the selective deletion of alloreactive T-cells, post-transplantation cyclophosphamide (PTCy) could modulate its negative impact on outcomes. We retrospectively compared acute leukemia patients receiving 10/10 or 9/10 HLA allele-matched UD-HCT with PTCy-GvHD prophylaxis between 2010 and 2017, reported to EBMT registry. The 100-day incidence of grade ≥2 and grade ≥3 aGvHD were comparable for 10/10 and 9/10 UD (28% versus 28%, p = 0.8 and 10% versus 8%, p = 0.5, respectively). The 2-year cGvHD and extensive cGvHD were similar between 10/10 and 9/10 UD (35% versus 44%, p = 0.2 and 21% versus 20%, p = 0.6, respectively). The 2-year nonrelapse mortality was 20% after 10/10 and 16% after 9/10 UD-HCT (p = 0.1). Relapse incidence at 2-year was 24% for 10/10 and 28% for 9/10 UD-HCT (p = 0.4). Leukemia-free survival at 2-year was the same for 10/10 and 9/10 UD (56 and 56%, p = 0.6, respectively), with comparable overall survival (62 and 59%, p = 0.9, respectively). Multivariate analysis showed no effect of HLA-matching on outcomes. An advanced disease status and patient disability remained the most important factors portending a worse survival. PTCy could alleviate the detrimental effect of HLA-allele mismatching in UD-HCT, potentially expanding the donor pool for acute leukemia patients.

摘要

HLA 匹配在很大程度上有助于非亲缘供者造血细胞移植(UD-HCT)的成功,但由于同种反应性 T 细胞的选择性缺失,移植后环磷酰胺(PTCy)可以调节其对结果的负面影响。我们回顾性比较了 2010 年至 2017 年报告给 EBMT 注册中心的接受 10/10 或 9/10 HLA 等位基因匹配 UD-HCT 联合 PTCy-GvHD 预防的急性白血病患者。10/10 和 9/10 UD 的 100 天发生率≥2 级和≥3 级移植物抗宿主病(aGvHD)相似(28%比 28%,p=0.8 和 10%比 8%,p=0.5)。10/10 和 9/10 UD 之间的 2 年慢性移植物抗宿主病(cGvHD)和广泛的 cGvHD 相似(35%比 44%,p=0.2 和 21%比 20%,p=0.6)。10/10 和 9/10 UD-HCT 的 2 年非复发死亡率分别为 20%和 16%(p=0.1)。2 年时的复发率分别为 10/10 和 9/10 UD-HCT 的 24%和 28%(p=0.4)。2 年时白血病无复发生存率在 10/10 和 9/10 UD 中相同(分别为 56%和 56%,p=0.6),总生存率相似(分别为 62%和 59%,p=0.9)。多变量分析显示 HLA 匹配对结果没有影响。晚期疾病状态和患者残疾仍然是预示生存状况较差的最重要因素。PTCy 可以减轻 UD-HCT 中 HLA 等位基因不匹配的不利影响,可能为急性白血病患者扩大供者群体。

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