Jurado Manuel, De La Mata Claudia, Ruiz-García Antonio, López-Fernández Elisa, Espinosa Olga, Remigia María José, Moratalla Lucía, Goterris Rosa, García-Martín Paloma, Ruiz-Cabello Francisco, Garzón Sebastián, Pascual María Jesús, Espigado Ildefonso, Solano Carlos
Department of Hematology, Complejo Hospitalario Universitario, Granada, Spain; Genyo Pfizer, Universidad de Granada, Junta de Andalucía, Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
Department of Hematology, Complejo Hospitalario Universitario, Granada, Spain.
Cytotherapy. 2017 Aug;19(8):927-936. doi: 10.1016/j.jcyt.2017.05.002. Epub 2017 Jun 26.
Despite the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the procedure is still associated with high toxicity in patients with refractory graft-versus-host disease (GvHD). Mesenchymal stromal cells (MSCs) are a new mode of therapy in the context of allo-HSCT. The objective of this study was to evaluate the safety and feasibility of the use of adipose tissue-derived MSCs (AT-MSCs) in patients with chronic GvHD.
Fourteen patients with moderate (n = 7) or severe (n = 7) chronic GvHD received 1 × 10/kg (group A, n = 9) or 3 × 10/kg (group B, n = 5) AT-MSCs with cyclosporine and prednisone as first-line therapy.
Ten of the 14 patients were able to continue under the protocol: 80% were in complete remission, and 100% were off of steroids at week 56. The remaining 4 patients either worsened from chronic GvHD (n = 3) or abandoned the study (n = 1). At the end of the study, 11 of 14 patients are alive (overall survival 71.4%, median survival of 45.3 weeks). No suspected unexpected serious adverse reactions occurred during the trial. Neither relapse of underlying disease nor mortality due to infection was observed in this cohort. Biological studies showed increased CD19, CD4 and tumor necrosis factor-α with a temporary decrease in natural killer cells.
AT-MSCs, in combination with immunosuppressive therapy, may be considered feasible and safe and likely would have an impact on the course of chronic GvHD. More studies are warranted to understand the potential benefits of AT-MSCs in these patients.
尽管异基因造血干细胞移植（allo-HSCT）疗效显著，但该手术对于难治性移植物抗宿主病（GvHD）患者仍具有高毒性。间充质基质细胞（MSCs）是allo-HSCT背景下的一种新治疗方式。本研究的目的是评估脂肪组织来源的间充质干细胞（AT-MSCs）用于慢性GvHD患者的安全性和可行性。
14例中度（n = 7）或重度（n = 7）慢性GvHD患者接受1×10/kg（A组，n = 9）或3×10/kg（B组，n = 5）的AT-MSCs，同时使用环孢素和泼尼松作为一线治疗。
14例患者中有10例能够继续接受该方案治疗：80%达到完全缓解，在第56周时100%停用类固醇药物。其余4例患者中，3例慢性GvHD病情恶化，1例退出研究。研究结束时，14例患者中有11例存活（总生存率71.4%，中位生存期45.3周）。试验期间未发生疑似意外严重不良反应。该队列中未观察到基础疾病复发或感染导致的死亡。生物学研究显示CD19、CD4和肿瘤坏死因子-α增加，自然杀伤细胞暂时减少。
AT-MSCs联合免疫抑制治疗可能被认为是可行和安全的，并且可能会对慢性GvHD的病程产生影响。有必要进行更多研究以了解AT-MSCs对这些患者的潜在益处。
