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非 T 细胞耗竭单倍体造血细胞移植治疗复发/难治性急性髓系白血病患者的细胞遗传学风险对结局的影响。

Impact of Cytogenetic Risk on Outcomes of Non-T-Cell-Depleted Haploidentical Hematopoietic Cell Transplantation in Patients with Relapsed or Refractory Acute Myeloid Leukemia.

机构信息

Division of Hematology, Sheba Medical Center, Tel Hashomer, Israel.

Sorbonne University, Sevice d'hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France; ALWP of the EBMT Paris office, Paris, France.

出版信息

Transplant Cell Ther. 2022 Nov;28(11):773.e1-773.e8. doi: 10.1016/j.jtct.2022.08.018. Epub 2022 Aug 27.

Abstract

Baseline cytogenetics and disease status are key factors predicting the outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with acute myeloid leukemia (AML). The importance of cytogenetic risk in patients with primary refractory or relapsed (R/R) AML undergoing haploidentical (Haplo) HCT is unknown. We studied the impact of cytogenetic risk in patients with R/R de novo AML with active disease who underwent non-T-cell-depleted Haplo-HCT with post-transplantation cyclophosphamide from 2010 to 2020. Four hundred forty patients with active disease at transplantation from the European Society for Blood and Marrow Transplantation database were analyzed (291 [66.1%] with intermediate-risk [AMLint] and 149 [44.1%] with adverse-risk cytogenetics [AMLadv]). Impact of baseline cytogenetic risk on various transplantation outcomes was evaluated. Pre-transplantation disease status was relapse in 48.1% and 26.8% and primary refractory in 51.9% and 73.2% of the patients with AMLint and AMLadv, respectively (P < .0001). Two-year leukemia-free survival (LFS, 35.5% versus 15.5%, P = .001) and overall survival (OS, 39.2% versus 20.1%, P = .001) were better in AMLint versus AMLadv. In multivariate analysis, the relapse rate was significantly higher (hazard ratio [HR] = 2.17 [95% confidence interval {CI} 1.57-3.0]) and LFS (HR = 1.71 [95% CI, 1.31-2.22]) and OS (HR = 1.69 [95% CI, 1.29-2.22]), significantly lower for patients with AMLadv compared to AMLint, conditioning intensity did not affect leukemia relapse rate. Non-relapse mortality (HR = 1.1 [95% CI, 0.7-1.74]) and graft-versus-host disease-free, relapse-free survival (HR = 1.37 [95% CI, 1.06-1.77]) did not differ significantly between the risk groups. Disease status before transplant (primary refractory versus relapsed) or conditioning intensity did not impact main transplant outcomes. Baseline cytogenetic risk remains a key prognostic factor for patients with R/R AML with persistent disease before non-T-cell-depleted Haplo-HCT.

摘要

在急性髓系白血病(AML)患者中,基线细胞遗传学和疾病状态是预测异基因造血细胞移植(HCT)结局的关键因素。在接受单倍体(Haplo)HCT 的原发性难治或复发(R/R)AML 患者中,细胞遗传学风险的重要性尚不清楚。我们研究了 2010 年至 2020 年间在有活动疾病的 R/R 初发 AML 患者中接受非 T 细胞耗竭性 Haplo-HCT 并接受移植后环磷酰胺治疗的患者中细胞遗传学风险的影响。从欧洲血液和骨髓移植学会数据库中分析了 440 例在移植时有活动疾病的患者(291 例[66.1%]为中危[AMLint],149 例[44.1%]为不良风险细胞遗传学[AMLadv])。评估了基线细胞遗传学风险对各种移植结局的影响。AMLint 和 AMLadv 患者的预处理疾病状态分别为复发 48.1%和 26.8%,以及原发性难治 51.9%和 73.2%(P<.0001)。AMLint 的 2 年无白血病生存率(LFS,35.5%对 15.5%,P=.001)和总生存率(OS,39.2%对 20.1%,P=.001)均优于 AMLadv。多变量分析显示,复发率显著升高(风险比[HR]2.17[95%置信区间{CI}1.57-3.0]),LFS(HR 1.71[95%CI,1.31-2.22])和 OS(HR 1.69[95%CI,1.29-2.22]),AMLadv 患者明显低于 AMLint,而预处理强度不影响白血病复发率。非复发死亡率(HR 1.1[95%CI,0.7-1.74])和移植物抗宿主病无复发生存率(HR 1.37[95%CI,1.06-1.77])在风险组之间无显著差异。移植前疾病状态(原发性难治性与复发)或预处理强度对主要移植结局无影响。在非 T 细胞耗竭性 Haplo-HCT 之前,有持续疾病的 R/R AML 患者的基线细胞遗传学风险仍然是一个关键的预后因素。

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