Behnam Sadeghi – Decidua stromal cells (DSC), new and promising source of stromal cells for acute inflammatory disorders

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There is an urgent need for effective therapy for severe acute GVHD. Results of GVHD therapies beyond 6 months are rarely reported. We here report a median follow-up of 4 years. We introduced mesenchymal stromal cells as therapy for severe acute GVHD, with a dramatic response in some, but not all patients. The placenta protects the haploidentical fetus from the mother’s immune system during pregnancy. We found that maternal stromal cells from the fetal membrane, so called decidua stromal cells (DSCs) were more immunosuppressive than other sources of stromal cells.

We treated 21 patients, median 49 years of age (range 1.6-72) for severe acute GVHD. All had biopsy proven gastro-intestinal GVHD. All were steroid refractory,11 after >7days or with progression and 10 after >3 days. DSCs were given at a median dose of 1.2 (0.9-2.9) x 106 cells/kg and 2(1-6) doses, given one week apart. Viability of frozen and thawed DSCs was 95% (89-100) and cell passage was 4 (2-4).

Complete resolution of GVHD was seen in 11 patients and 10 had a partial response. The cumulative incidence of chronic GVHD was 52%. Six had mild, 4 moderate and one severe, based on the NIH overall GVHD severity scoring. Nine patients died, 3 from relapse, 1 acute GVHD and septicemia, 1 zygomycetes infection, 1 liver insufficiency, 1 cerebral hemorrhage, 1multiorgan failure and 1 chronic GVHD with obstructive bronchiolitis. Four years transplant related mortality was 28.6% and overall survival was 57%. Survival was not significantly worse (p=0.33) than 66% for all 293 patients undergoing allogeneic hematopoietic cell transplantation during the same period 2012-2015.

To conclude, DSCs seems to be a promising new cell based therapy for severe acute GVHD and other acute inflammatory disorders. Randomized trials are under way.

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