Table_3_Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion.pdf

Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with several potentially lethal complications. Higher levels of CD3+ T-cells in the graft have been associated with increased risk of graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia effect and reduced infections. To tackle post-transplant complications, donor lymphocyte infusions have been used but with an increased risk of GVHD. To reduce this risk, we performed depletion of αβ T-cells and treated 12 patients post-HSCT suffering from infections and/or poor immune reconstitution. The αβ T-cell depleted cell products were characterized by flow cytometry. The median log depletion of αβ T-cells was −4.3 and the median yield of γδ T-cells was 73.5%. The median CD34+ cell dose was 4.4 × 106/kg. All 12 patients were alive 3 months after infusion and after 1 year, two patients had died. No infusion-related side effects were reported and no severe acute GVHD (grade III-IV) developed in any patient post-infusion. Overall, 3 months after infusion 11 out of 12 patients had increased levels of platelets and/or granulocytes. In conclusion, we describe the use of αβ T-cell depleted products as stem cell boosters with encouraging results.

异基因造血干细胞移植（HSCT）与多种潜在致命并发症相关。移植物中CD3+ T细胞的水平较高已被与移植物抗宿主病（GVHD）风险增加相关联，但也与有益的移植物抗白血病效应及感染减少相关。为了应对移植后的并发症，曾使用供体淋巴细胞输注，但这也增加了GVHD的风险。为降低此风险，我们对12例在HSCT后因感染和/或免疫功能重建不良而接受治疗的αβ T细胞进行了耗竭处理。通过流式细胞术对αβ T细胞耗竭的细胞产品进行了表征。αβ T细胞的平均对数耗竭水平为−4.3，γδ T细胞的平均产量为73.5%。CD34+细胞的平均剂量为4.4 × 106/kg。所有12名患者在输注后3个月均存活，而1年后，两名患者死亡。未报告输注相关的不良反应，且在任何患者中均未发生严重急性GVHD（III-IV级）。总体而言，在输注后3个月，12名患者中的11名血小板和/或粒细胞水平有所升高。总之，本文描述了αβ T细胞耗竭产品作为干细胞增强剂的应用，并取得了令人鼓舞的结果。