Chakupurakal Geothy, García-Márquez María Alejandra, Shimabukuro-Vornhagen Alexander, Theurich Sebastian, Holtick Udo, Hallek Michael, Scheid Christof, von Bergwelt-Baildon Michael
Interventional Immunology Group, Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Max-Planck-Institute for Metabolism, Research, Cologne, Germany.
Eur J Haematol. 2016 Aug;97(2):121-7. doi: 10.1111/ejh.12691. Epub 2015 Nov 16.
Steroid-refractory graft-versus-host disease (GvHD) is a complication following an allogeneic stem cell transplantation with limited therapeutic options. Studies have shown a response in up to 80% of patients with this condition after treatment with the CD25 monoclonal antibody, basiliximab. Despite the good responses to treatment, around 50% of the patients experience recurrence of their GvHD symptoms 4-6 wk following cessation of therapy. The in vivo changes in the following treatment with this antibody have not been elucidated so far. We treated 14 patients with severe steroid-refractory GvHD with basiliximab weekly for 4 wk and monitored the changes in the T-, B-, NK- and dendritic cell subsets over this time period. The overall response to treatment was 92% (13/14) with 50% (7/14) achieving a complete response. Fifty four percentage (7/13) of the patients who responded showed recurrence of their GvHD symptoms. Contrary to expectations, our observations showed a significant depletion of the regulatory T-cell subset following treatment. Our findings suggest that the undesirable depletion of the regulatory T cells along with the CD25(+) acute inflammatory cells might be responsible for the high incidence of GvHD recurrence in this cohort of patients.
类固醇难治性移植物抗宿主病(GvHD)是异基因干细胞移植后的一种并发症,治疗选择有限。研究表明,使用CD25单克隆抗体巴利昔单抗治疗后,高达80%的此类患者会出现反应。尽管治疗反应良好,但约50%的患者在治疗停止后4 - 6周会出现GvHD症状复发。迄今为止,尚未阐明该抗体治疗后体内的变化情况。我们对14例严重类固醇难治性GvHD患者每周使用巴利昔单抗治疗4周,并在此期间监测T细胞、B细胞、NK细胞和树突状细胞亚群的变化。治疗的总体反应率为92%(13/14),其中50%(7/14)达到完全缓解。有反应的患者中有54%(7/13)出现了GvHD症状复发。与预期相反,我们的观察结果显示治疗后调节性T细胞亚群显著减少。我们的研究结果表明,调节性T细胞与CD25(+)急性炎症细胞的不良减少可能是该组患者GvHD复发率高的原因。