| Popis: |
Graft-versus-host disease (GVHD) remains as one of the most important complications after allogeneic hematopoietic stem cell transplantation (allo-SCT) and there is no definitive second-line therapy for steroid-refractory patients both in acute and chronic GVHD. Mesenchymal stromal cells (MSC) have emerged as an attractive potential therapeutic tool in this setting, based on their potent immunomodulatory capacity. MSC are able to modulate the activation, proliferation, and/or maturation of T-cells, B-cells, NK cells, dendritic cells, neutrophils, etc., and expand the proportion of other immunomodulatory cells (e.g., regulatory T-cells, M2 macrophages) both in vitro and in vivo. All these mechanisms favor their potential application in GVHD, where deregulation of the adoptive and innate immune systems together with a high pro-inflammatory microenvironment induces the typically observed damage in the target organs. In this chapter, we discuss the clinical experience on the use of MSC both for the prevention and treatment of GVHD. The largest experience has been generated in the treatment of steroid-refractory acute GVHD, where MSC have demonstrated in numerous phase II trials relatively high response rates, including complete responses, which correlate with a significant benefit in overall survival. Nevertheless, there are few phase III trial evidences of the beneficial effects of MSC and some reported results have been disappointing. Fortunately, new information is coming from these randomized trials that may lead to additional MSC approvals in some countries, especially for pediatric patients. There are many questions that have not been answered yet, covering the optimal culture and expansion methods, the need of cryopreservation and/or refreshing the cryopreserved products before administration, the best timing, and the number of doses and their intervals, among others, including the need of a biological assay or biomarker that may predict a clinical response to MSC before initiating the treatment. |
