Abstract
Mesenchymal stromal cells (MSCs) are rare precursors in all organs of the body. MSCs have profound anti-inflammatory effects and reduce alloreactivity in vitro and in vivo. In pediatric allogeneic hematopoietic cell transplantation (HCT), MSCs have mainly been used to treat acute graft-versus-host disease (GVHD). MSCs are commercially available for this indication in Canada, Japan, and New Zeeland. More rare indications for MSCs in pediatric patients include graft failure and chronic GVHD. MSCs from bone marrow, adipose tissue, umbilical cord, Wharton's jelly, placenta tissue, and decidua have been used, but the optimal clinical stromal cell source has not been compared in clinical trials. More experimental clinical indications using MSCs, such as sepsis, acute respiratory distress syndrome, hemorrhages, pneumo-mediastinum, and neuroinflammation have primarily been explored in animal models or adult HCT patients. MSCs have almost no if any side-effects. In this pilot study we report the outcome of six children treated with decidua stromal cells (DSCs) for steroid refractory acute GVHD. At 6 months, complete response was seen in four patients and partial response in two patients. One child with high-risk ALL died from relapse and a boy with sickle cell disease died from a cerebral hemorrhage. Five-year survival was 67% and all survivors showed a Lansky score of 100%. To conclude, MSCs from various organs are well-tolerated and have shown an encouraging outcome for acute GVHD in pediatric patients.
Highlights
Hematopoietic cell transplantation (HCT) is an established treatment for children with both malignant and non-malignant hematopoietic diseases and inborn errors of metabolism [1,2,3,4]
There is a 5-year survival of 67%. This is only a small series of pediatric patients treated for acute graft-versus-host disease (GVHD), it still holds some promise
Children have a better outcome than adults after hematopoietic cell transplantation (HCT) and this is striking in patients with severe acute GVHD [6]
Summary
Hematopoietic cell transplantation (HCT) is an established treatment for children with both malignant and non-malignant hematopoietic diseases and inborn errors of metabolism [1,2,3,4]. A majority of the patients developed acute GVHD, with a considerable mortality, even if this was significantly lower in children compared to adults [6]. Cortisone is first-line therapy for acute GVHD [10] and almost all immunosuppressive therapies are used as a secondary treatment with varying degrees of success [11]. We introduced mesenchymal stromal cells (MSCs) as a new therapy for acute GVHD [13, 14]. They stain positive for CD29, CD73, CD90, CD105, and CD166 They are negative for hematopoietic markers, CD34, CD45, and CD14. They are not true stem cells because they cannot regenerate and maintain a whole tissue compartment. MSCs do not appear to be long lived and have been demonstrated in the circulation only shortly after infusion into patients who underwent autologous HCT for breast cancer [18]
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