No abstract

Mesenchymal stromal cells (MSCs) as a pharmaceutical for ailments characterized by pathogenic autoimmune, alloimmune and inflammatory processes now cover the spectrum of early- to late-phase clinical trials in both industry and academic sponsored studies. There is a broad consensus that despite different tissue sourcing and varied culture expansion protocols, human MSC-like cell products likely share fundamental mechanisms of action mediating their anti-inflammatory and tissue repair functionalities. Identification of functional markers of potency and reduction to practice of standardized, easily deployable methods of measurements of such would benefit the field. This would satisfy both mechanistic research as well as development of release potency assays to meet Regulatory Authority requirements for conduct of advanced clinical studies and their eventual registration. In response to this unmet need, the International Society for Cellular Therapy (ISCT) addressed the issue at an international workshop in May 2015 as part of the 21st ISCT annual meeting in Las Vegas. The scope of the workshop was focused on discussing potency assays germane to immunomodulation by MSC-like products in clinical indications targeting immune disorders. We here provide consensus perspective arising from this forum. We propose that focused analysis of selected MSC markers robustly deployed by in vitro licensing and metricized with a matrix of assays should be responsive to requirements from Regulatory Authorities. Workshop participants identified three preferred analytic methods that could inform a matrix assay approach: quantitative RNA analysis of selected gene products; flow cytometry analysis of functionally relevant surface markers and protein-based assay of secretome. We also advocate that potency assays acceptable to the Regulatory Authorities be rendered publicly accessible in an “open-access” manner, such as through publication or database collection.

A targeted monitoring strategy among patients at a high risk of EBV-associated PTLD might be helpful to decrease the risk of development of PTLD. However, larger prospective studies are needed to verify this hypothesis.

Summary:The effect of granulocyte colony-stimulating factor (G-CSF), given after transplantation, was studied in 155 patients transplanted with haematopoietic stem cells (HSCT) from HLA-identical sibling donors at Huddinge University Hospital between 1993 and 2001. Only patients with haematological malignancies were included. Conditioning consisted of total-body irradiation in 118 and busulphan in 37 patients. They were all given methotrexate combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Of the 155 patients, 66 (43%) received G-CSF after HSCT. Those given G-CSF had a significantly shorter time to neutrophil engraftment (Po0.001). G-CSF treatment had no effect on erythrocyte transfusions, platelet engraftment and infections. However, patients treated with G-CSF had a significantly higher incidence of grades II-IV acute GVHD than those not given this treatment (34 vs 9%, Po0.001). The multivariate analysis showed that the effect of G-CSF was independent of other known risk factors for grades II-IV acute GVHD. Death from GVHD occurred in four and two cases (P ¼ 0.06) in the two groups, respectively. The cumulative incidences of transplant-related mortality, survival, chronic GVHD, relapse and relapse-free survival were similar in both groups. In conclusion, G-CSF given after HLA-identical sibling HSCT was associated with a higher risk of grades II-IV acute GVHD, but not transplant-related mortality.