Autologous stem cell transplantation (ASCT) is a potentially curative therapy but requires collection of sufficient blood stem cells (PBSC). Up to 40 % of patients with multiple myeloma (MM) fail to collect an optimum number of PBSC using filgrastim only and often require costly plerixafor rescue. The nonsteroidal anti-inflammatory drug meloxicam mobilizes PBSC in mice, nonhuman primates and normal volunteers, and has the potential to attenuate mobilization-induced oxidative stress on stem cells. In a single-center study, we evaluated whether a meloxicam regimen prior to filgrastim increases collection and/or homeostasis of CD34⁺ cells in MM patients undergoing ASCT. Mobilization was not significantly different with meloxicam in this study; a median of 2.4 × 10⁶ CD34⁺ cells/kg were collected in the first apheresis and 9.2 × 10⁶ CD34⁺ cells/kg were collected overall for patients mobilized with meloxicam-filgrastim, versus 4.1 × 10⁶ in first apheresis and 7.2 × 10⁶/kg overall for patients mobilized with filgrastim alone. CXCR4 expression was reduced on CD34⁺ cells and a higher CD4⁺/CD8⁺ T-cell ratio was observed after mobilization with meloxicam-filgrastim. All patients treated with meloxicam-filgrastim underwent ASCT, with neutrophil and platelet engraftment similar to filgrastim alone. RNA sequencing of purified CD34⁺ cells from 22 MM patients mobilized with meloxicam-filgrastim and 10 patients mobilized with filgrastim only identified > 4,800 differentially expressed genes (FDR < 0.05). Enrichment analysis indicated significant attenuation of oxidative phosphorylation and translational activity, possibly mediated by SIRT1, suggesting meloxicam may counteract oxidative stress during PBSC collection. Our results indicate that meloxicam was a safe, low-cost supplement to filgrastim mobilization, which appeared to mitigate HSPC oxidative stress, and may represent a simple means to lessen stem cell exhaustion and enhance graft quality.

Graphical Abstract

中文翻译：

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美洛昔康和非格司亭可减少多发性骨髓瘤患者自体外周血干细胞动员期间造血祖细胞的氧化应激

自体干细胞移植 (ASCT) 是一种潜在的治愈性疗法，但需要收集足够的血液干细胞 (PBSC)。多达 40% 的多发性骨髓瘤 (MM) 患者仅使用非格司亭未能收集到最佳数量的 PBSC，并且通常需要昂贵的普乐沙进行抢救。非甾体抗炎药美洛昔康可动员小鼠、非人类灵长类动物和正常志愿者的 PBSC，并有可能减轻动员诱导的干细胞氧化应激。在一项单中心研究中，我们评估了在非格司亭之前使用美洛昔康方案是否会增加接受 ASCT 的 MM 患者CD34 ^{+细胞的收集和/或稳态。}在这项研究中，美洛昔康的动员没有显着差异；中位数为 2.4 × 10 ⁶ CD34 ⁺在第一次单采术中收集了细胞/kg，对于使用美洛昔康-非格司亭的患者，总体收集了 9.2 × 10 ^{6 个CD34} +^细胞/kg，而在第一次单采术中收集了 4.1 × 10 ⁶ ，对于使用单独使用非格司亭。在用美洛昔康-非格司亭动员后，CD34 ⁺细胞上的 CXCR4 表达降低，并且观察到更高的 CD4 ⁺ /CD8 ⁺ T 细胞比率。所有接受美洛昔康-非格司亭治疗的患者均接受了 ASCT，中性粒细胞和血小板植入与单独使用非格司亭相似。纯化 CD34 ^{+的 RNA 测序}来自用美洛昔康-非格司亭动员的 22 名 MM 患者和用非格司亭动员的 10 名患者的细胞仅鉴定了 > 4,800 个差异表达基因（FDR < 0.05）。富集分析表明氧化磷酸化和翻译活性显着减弱，可能由 SIRT1 介导，表明美洛昔康可能在 PBSC 收集过程中抵消氧化应激。我们的研究结果表明，美洛昔康是一种安全、低成本的非格司亭动员补充剂，它似乎可以减轻 HSPC 氧化应激，并可能代表一种减少干细胞耗竭和提高移植质量的简单方法。

图形概要