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巨细胞病毒、社会经济地位、种族和民族对单倍体造血移植后结局的影响研究。

An Examination of Cytomegalovirus, Socioeconomic Status, Race, and Ethnicity on Outcomes after Haploidentical Hematopoietic Transplantation.

机构信息

Department of Medical Oncology, The Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania.

Pharmacology and Experimental Therapeutics, The Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania.

出版信息

Transplant Cell Ther. 2021 Apr;27(4):327.e1-327.e11. doi: 10.1016/j.jtct.2020.11.017. Epub 2020 Dec 16.

Abstract

Previous analyses of the effects of race and socioeconomic status (SES) on outcomes after hematopoietic stem cell transplantation (HSCT) have suggested that minority populations and those in disadvantaged groups have inferior outcomes. However, the results of these studies have been inconsistent, potentially due to a multitude of factors, both medical and nonmedical, that have confounded results. In haploidentical (HI) HSCT, an expanding approach with the potential to enfranchise more minority patients, data on the effect of race and SES on outcomes are very limited. To identify and potentially correct factors that negatively impact outcomes after HI HSCT in disadvantaged groups at our institution, we performed a retrospective, multivariable analysis of the impact of race and SES as single and combined variables on HI HSCT outcomes of relapse, transplantation-related mortality, acute and chronic graft-versus-host disease (GVHD), and overall survival (OS). In addition to controlling for race and SES, all patients had HI donors and were treated with the same 2-step approach, with consistent T cell dosing and GVHD prophylaxis to further reduce the impact of confounders in this complex area. The study cohort of 239 patients was 71% Caucasian, 19.7% African American, 4.6% Hispanic, and 4.2% Asian. The majority of minority patients were in areas of higher deprivation (P = .001) and had the highest incidence of cytomegalovirus (CMV) seropositivity (P = .001) and the lowest likelihood of possessing a CMV immunodominant (IMD) allele (P = .001), which was previously associated with an OS benefit. Positive CMV serostatus was highly linked to post-transplantation CMV reactivation (P = .001) which was associated with higher relapse rates (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.06 to 2.30; P = .026), higher TRM (HR, 2.10; 95% CI, 1.09 to 4.05; P = .027), and lower OS (HR, 1.77; 95% CI, 1.18 to 2.65; P = .006). The lack of a CMV IMD allele largely replicated the results of CMV reactivation on HSCT results. Although race and SES did not directly correlate with either OS or relapse incidence, non-Caucasians in a more disadvantaged group had a higher incidence of chronic GVHD (HR, 2.55; 95% CI, 1.08 to 6.01; P = .033) compared with Caucasians and minorities in less disadvantaged groups. Regardless of SES, minorities had a lower incidence of acute GVHD than Caucasians in a more advantaged SES group (HR, 0.52; 95% CI, 0.30 to 0.90; P = .020). The primary finding of this study is that CMV reactivation was the major driver of mortality after HI HSCT. CMV reactivation may have be associated with poor HSCT outcomes in HI HSCT recipients in disadvantaged areas, most of whom were minorities. The data suggest that the prevention of post-transplantation CMV reactivation possibly could have a major impact on HI HSCT outcomes, especially in minority recipients. The finding of different GVHD manifestations between races are intriguing and merits further study.

摘要

先前对造血干细胞移植 (HSCT) 后种族和社会经济地位 (SES) 对结果影响的分析表明,少数群体和处于不利地位的群体的结果较差。然而,这些研究的结果不一致,可能是由于多种医学和非医学因素混淆了结果。在单倍体相合 (HI) HSCT 中,一种扩展的方法有可能使更多的少数族裔患者受益,但关于种族和 SES 对 HI HSCT 结果的影响的数据非常有限。为了确定并可能纠正我们机构中弱势群体 HI HSCT 后负面结果的影响因素,我们对种族和 SES 作为单一和组合变量对 HI HSCT 结果(复发、移植相关死亡率、急性和慢性移植物抗宿主病 [GVHD]、总生存率 [OS])的影响进行了回顾性、多变量分析。除了控制种族和 SES 之外,所有患者都有 HI 供体,并采用相同的两步治疗方法,进行一致的 T 细胞剂量和 GVHD 预防,以进一步减少这一复杂领域混杂因素的影响。这项研究的 239 名患者队列中,71%为白种人,19.7%为非裔美国人,4.6%为西班牙裔,4.2%为亚裔。大多数少数族裔患者处于贫困程度较高的地区(P = 0.001),CMV 血清阳性率最高(P = 0.001),拥有 CMV 免疫显性(IMD)等位基因的可能性最低(P = 0.001),这与 OS 获益之前有关联。CMV 阳性状态与移植后 CMV 再激活高度相关(P = 0.001),这与更高的复发率(危险比 [HR],1.56;95%置信区间 [CI],1.06 至 2.30;P = 0.026)、更高的 TRM(HR,2.10;95%CI,1.09 至 4.05;P = 0.027)和更低的 OS(HR,1.77;95%CI,1.18 至 2.65;P = 0.006)相关。缺乏 CMV IMD 等位基因在很大程度上复制了 CMV 再激活对 HSCT 结果的影响。尽管种族和 SES 与 OS 或复发发生率没有直接相关性,但处于较不利群体的非白种人慢性 GVHD 的发生率较高(HR,2.55;95%CI,1.08 至 6.01;P = 0.033)与白种人和 SES 较低的少数群体相比。无论 SES 如何,与 SES 较高的白种人相比, SES 较低的少数族裔急性 GVHD 的发生率较低(HR,0.52;95%CI,0.30 至 0.90;P = 0.020)。这项研究的主要发现是 CMV 再激活是 HI HSCT 后死亡的主要驱动因素。CMV 再激活可能与 HI HSCT 受者在贫困地区的不良 HSCT 结果有关,其中大多数是少数民族。数据表明,预防移植后 CMV 再激活可能对 HI HSCT 结果产生重大影响,尤其是在少数族裔受者中。种族之间不同 GVHD 表现的发现很有趣,值得进一步研究。

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