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BMT CTN 0803/AMC 071 试验中接受自体造血干细胞移植的 HIV 相关淋巴瘤患者的免疫恢复。

Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial.

机构信息

Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States.

Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States.

出版信息

Front Immunol. 2021 Sep 3;12:700045. doi: 10.3389/fimmu.2021.700045. eCollection 2021.

Abstract

We report a first in-depth comparison of immune reconstitution in patients with HIV-related lymphoma following autologous hematopoietic cell transplant (AHCT) recipients (n=37, lymphoma, BEAM conditioning), HIV(-) AHCT recipients (n=30, myeloma, melphalan conditioning) at 56, 180, and 365 days post-AHCT, and 71 healthy control subjects. Principal component analysis showed that immune cell composition in HIV(+) and HIV(-) AHCT recipients clustered away from healthy controls and from each other at each time point, but approached healthy controls over time. Unsupervised feature importance score analysis identified activated T cells, cytotoxic memory and effector T cells [higher in HIV(+)], and naïve and memory T helper cells [lower HIV(+)] as a having a significant impact on differences between HIV(+) AHCT recipient and healthy control lymphocyte composition (p<0.0033). HIV(+) AHCT recipients also demonstrated lower median absolute numbers of activated B cells and lower NK cell sub-populations, compared to healthy controls (p<0.0033) and HIV(-) AHCT recipients (p<0.006). HIV(+) patient T cells showed robust IFNγ production in response to HIV and EBV recall antigens. Overall, HIV(+) AHCT recipients, but not HIV(-) AHCT recipients, exhibited reconstitution of pro-inflammatory immune profiling that was consistent with that seen in patients with chronic HIV infection treated with antiretroviral regimens. Our results further support the use of AHCT in HIV(+) individuals with relapsed/refractory lymphoma.

摘要

我们报告了首例对接受自体造血细胞移植(AHCT)的 HIV 相关淋巴瘤患者(n=37,淋巴瘤,BEAM 预处理)、HIV(-)AHCT 患者(n=30,骨髓瘤,马法兰预处理)在 AHCT 后 56、180 和 365 天以及 71 名健康对照者的免疫重建进行的深入比较。主成分分析表明,HIV(+)和 HIV(-)AHCT 受者的免疫细胞组成在每个时间点都远离健康对照者,彼此聚类,但随着时间的推移逐渐接近健康对照者。无监督特征重要性评分分析确定了活化 T 细胞、细胞毒性记忆和效应 T 细胞[在 HIV(+)中更高]以及幼稚和记忆 T 辅助细胞[在 HIV(+)中更低]对 HIV(+)AHCT 受者和健康对照者淋巴细胞组成差异有显著影响(p<0.0033)。与健康对照者(p<0.0033)和 HIV(-)AHCT 受者(p<0.006)相比,HIV(+)AHCT 受者也表现出活化 B 细胞和 NK 细胞亚群的中位数绝对数量较低。与健康对照者相比,HIV(+)患者的 T 细胞对 HIV 和 EBV 回忆抗原表现出强烈的 IFNγ产生。总体而言,HIV(+)AHCT 受者,但不是 HIV(-)AHCT 受者,表现出促炎免疫谱的重建,与接受抗逆转录病毒治疗方案治疗的慢性 HIV 感染患者相似。我们的研究结果进一步支持在复发/难治性淋巴瘤的 HIV(+)个体中使用 AHCT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f64c/8446430/4a95b98d5b1f/fimmu-12-700045-g001.jpg

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