Müller Ingo, Kordowich Sandra, Holzwarth Christina, Isensee Gesa, Lang Peter, Neunhoeffer Felix, Dominici Massimo, Greil Johann, Handgretinger Rupert
Department of General Pediatrics, Hematology and Oncology, University Children's Hospital Tübingen, Hoppe-Seyler-St. 1, 72076, Tubigen, Germany.
Blood Cells Mol Dis. 2008 Jan-Feb;40(1):25-32. doi: 10.1016/j.bcmd.2007.06.021. Epub 2007 Sep 14.
Multipotent mesenchymal stromal cells (MSC) have immunomodulatory effects. The aim of this study was to demonstrate safety and feasibility of MSC transfusion in pediatric patients who had undergone allogeneic stem cell transplantation from MMFD, MUD, MMUD and MSD. Patients with posttransplant complications based on deregulated immune effector cells who may benefit from an immunomodulatory effect of MSC had been selected. MSC were isolated from the hematopoietic stem cell donors in five cases and from a third party parental donor in two cases. We transfused ex vivo-expanded MSC in 11 doses into seven pediatric patients. Cell doses were escalated based on availability from 0.4x10(6) to 3.0x10(6) per kg bodyweight No adverse effects were detected with a maximum follow-up of 29 months. One out of three patients showed slight improvement of chronic GVHD. Two patients with severe acute GvHD did not progress to cGvHD. One patient received MSC to stabilize graft function after secondary haploidentical transplantation. One patient recovered from trilineage failure due to severe hemophagocytosis. This is the first case of a pediatric patient treated with MSC for trilineage failure after haploidentical stem cell transplantation from her father. We report the first series of 11 transfusions of expanded MSC in pediatric patients with immunological complications after allogeneic transplantation. Transfusion of MSC was safe and encouraging improvements in some patients were observed.
多能间充质基质细胞（MSC）具有免疫调节作用。本研究的目的是证明在接受来自单倍体相合非血缘供者（MMFD）、非血缘供者（MUD）、单倍体相合血缘供者（MMUD）和同胞全相合供者（MSD）的异基因干细胞移植的儿科患者中输注MSC的安全性和可行性。选择了那些因免疫效应细胞失调而出现移植后并发症且可能从MSC的免疫调节作用中获益的患者。在5例中，MSC从造血干细胞供者中分离，在2例中从第三方亲代供者中分离。我们将体外扩增的MSC分11次剂量输注给7名儿科患者。根据可获得性，细胞剂量从每千克体重0.4×10⁶逐步增加到3.0×10⁶。在最长29个月的随访中未检测到不良反应。3名患者中有1名慢性移植物抗宿主病（GVHD）略有改善。2名严重急性GVHD患者未进展为慢性GVHD。1名患者在二次单倍体相合移植后接受MSC以稳定移植物功能。1名患者因严重噬血细胞综合征从三系造血衰竭中恢复。这是首例接受MSC治疗单倍体相合干细胞移植后三系造血衰竭的儿科患者，该移植来自其父亲。我们报告了首例在异基因移植后有免疫并发症的儿科患者中进行11次扩增MSC输注的系列病例。输注MSC是安全的，并且在一些患者中观察到了令人鼓舞的改善。
