Long-term follow up of a pilot study using placenta derived decidua stromal cells for severe acute graft versus host diseases

Abstract

Background & Aim There is a need for effective therapy with few side effects for severe acute graft-versus-host disease (GVHD). The placenta protects the fetus from the mother's haploidentical immune system during pregnancy. We report that maternal stromal cells from the fetal membrane, so called decidua stromal cells (DSCs) were more immunosuppressive than other sources of stromal cells. Methods, Results & Conclusion We prospectively treated 21 patients, median 49 years of age (range 1.6-72) for grades II-IV acute GVHD. All had biopsy-proven gastrointestinal GVHD. Majority of patients were either steroid-refractory or had progressive GVHD, 11 patients after >7 days or with progression after 3 days and 10 were refractory to steroid after >3 days. We used an improved protocol where DSCs were thawed and infused in a buffer with 5% human albumin. DSCs were given at a median dose of 1.2 (0.9-2.9) × 106 cells/kg with a median of 2 (1-6) doses, given one week apart. Viability of thawed DSCs was 93% (69-100) 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 1 severe using the NIH overall chronic GVHD severity scoring. Nine patients died, 3 from relapse, 1 acute GVHD and septicemia, 1 zygomycet infection, 1 liver insufficiency, 1 cerebral hemorrhage, 1 multi-organ failure and 1 chronic GVHD with obstructive bronchiolitis. Four year transplant-related mortality was 28.6% and overall survival was 57%. Survival was similar (p=0.33) compared to all 293 patients that underwent allogeneic hematopoietic cell transplantation during the same period 2012-2015, with a 66 % overall survival. To conclude, DSCs seem to induce a promising long-term outcome for acute GVHD grades II-IV. Randomized trials are under way. There is a need for effective therapy with few side effects for severe acute graft-versus-host disease (GVHD). The placenta protects the fetus from the mother's haploidentical immune system during pregnancy. We report that maternal stromal cells from the fetal membrane, so called decidua stromal cells (DSCs) were more immunosuppressive than other sources of stromal cells. We prospectively treated 21 patients, median 49 years of age (range 1.6-72) for grades II-IV acute GVHD. All had biopsy-proven gastrointestinal GVHD. Majority of patients were either steroid-refractory or had progressive GVHD, 11 patients after >7 days or with progression after 3 days and 10 were refractory to steroid after >3 days. We used an improved protocol where DSCs were thawed and infused in a buffer with 5% human albumin. DSCs were given at a median dose of 1.2 (0.9-2.9) × 106 cells/kg with a median of 2 (1-6) doses, given one week apart. Viability of thawed DSCs was 93% (69-100) and cell passage was 4 (2-4).