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未处理的单倍体相合与 HLA 匹配的同胞异基因造血干细胞移植治疗复发/难治性急性髓系白血病:一项代表 EBMT 的 ALWP 的回顾性研究。

Unmanipulated haploidentical versus HLA-matched sibling allogeneic hematopoietic stem cell transplantation in relapsed/refractory acute myeloid leukemia: a retrospective study on behalf of the ALWP of the EBMT.

机构信息

Hematology Department, Hôpital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire, Paris, France.

Hematology Department, Federico II University, Naples, Italy.

出版信息

Bone Marrow Transplant. 2019 Sep;54(9):1499-1510. doi: 10.1038/s41409-019-0459-7. Epub 2019 Feb 4.

Abstract

Refractory or relapsed acute myeloid leukemia (R/R-AML) has poor prognosis. Allogeneic hematopoietic stem-cell transplantation (HSCT) may provide cure in this scenario. We compared outcomes of HSCT from HLA-identical (HLA-id, n = 1654) sibling or haploidentical (Haplo, n = 389) donors in patients with R/R-AML, performed during the period 2007-2015. The Haplo group included patients receiving an unmanipulated graft (post-transplant cyclophosphamide, n = 278; in vivo T-cell depletion, n = 95; or both, n = 16). Median age at HSCT was 52 (range 18-74) years. Median follow-up was 16 and 22 months for HLA-id sibling and Haplo recipients, respectively (p = 0.11). Compared to MSD, Haplo HSCT were performed more recently (2013 vs 2011, p < 0.01), at longer interval from diagnosis (7 vs 5 months, p < 0.01), more frequently using bone marrow as stem cell source (47% vs 8%, p < 0.01) and with a reduced intensity conditioning regimen (50% vs 43%, p = 0.03). Engraftment was higher (93% vs 83%, p < 0.01) in HLA-id sibling. In multivariate analysis, Haplo HSCT was associated with lower GVHD/relapse-free survival, inferior LFS and OS and higher NRM, mainly due to a higher rate of infections (41% vs 25%, p < 0.01). For R/R-AML, HLA-id sibling donors remain the gold standard, when available, due to higher mortality in Haplo without significant gain in disease control.

摘要

难治或复发急性髓系白血病(R/R-AML)预后差。异基因造血干细胞移植(HSCT)可能为此提供治愈机会。我们比较了 2007 年至 2015 年间接受 HLA 匹配(HLA-id,n=1654)同胞或单倍体(Haplo,n=389)供者 HSCT 的 R/R-AML 患者的结果。Haplo 组包括接受未处理移植物(移植后环磷酰胺,n=278;体内 T 细胞耗竭,n=95;或两者均有,n=16)的患者。HSCT 时的中位年龄为 52 岁(18-74 岁)。HLA-id 同胞和 Haplo 受体的中位随访时间分别为 16 个月和 22 个月(p=0.11)。与 MSD 相比,Haplo HSCT 进行得更近(2013 年比 2011 年,p<0.01),从诊断到移植的时间间隔更长(7 个月比 5 个月,p<0.01),更常使用骨髓作为干细胞来源(47%比 8%,p<0.01),且强度更低的预处理方案(50%比 43%,p=0.03)。同胞 HLA-id 的植入率更高(93%比 83%,p<0.01)。多变量分析显示,Haplo HSCT 与较低的 GVHD/无复发存活率、较低的 LFS 和 OS 以及较高的 NRM 相关,主要是由于感染率较高(41%比 25%,p<0.01)。对于 R/R-AML,在有条件的情况下,HLA-id 同胞供者仍然是金标准,因为 Haplo 的死亡率更高,而疾病控制没有明显改善。

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