Decidual Stromal Cells As Treatment for Acute Graft Versus Host Disease

Graft versus host disease (GvHD) is a common and severe complication after allogeneic stem cell transplantation. During pregnancy, the placenta and the fetal membranes function as an immunological barrier, protecting the fetus from the mother's immune system. We have isolated stromal cells from the decidual layer of term placentas. These decidual stromal cells (DSCs) are of maternal origin, and strongly inhibit the alloreactivity of T-cells in vitro. The effect is mainly contact dependent, and decreases the production of several key cytokines involved in the cytokine storm promoting the continuation of GvHD.

To investigate the effect of DSCs on acute GvHD we enrolled 32 patients diagnosed with acute GvHD grade 2-4 and clinically non-responsive to standard therapy. The protocol was changed after 17 patients, the DSCs were then thawed and infused in infusion solution with albumin instead of AB-plasma and given repeatedly and earlier upon diagnosis. This led to the formation of two treatment groups (group 1 n=17 and group 2 n=15), which were compared to matched historical controls (n=54). We also performed a retrospectively corrected analysis of steroid refractivity at day 7 after start of corticosteroids in the different groups.

Group 1 received a median of 1 (range 1-5) infusion on day 11 (range 1-31) after standard treatment compared to group 2, who received a median of 2 infusions (range 1-4, p<0,05) on day 6 (range 0-26, ns). No adverse events related to the treatment were observed. At 4 weeks after treatment, 60% of the patients in group 1 hade responded to the treatment. In contrast, all patients in group 2 responded (p<0,05). All patients in the treatment groups received fungal prophylaxis.

The overall cumulative survival (OS) at 365 days was 78% for group 2, as compared to 47% for group 1 and 28% for the controls (p<0.001). When the groups were corrected for steroid-refractivity, the OS was 76% for group 2, 38% for group 1 and 6% for the controls (p<0.001). In the control group, the risk of dying from GvHD was 51%, compared to 48% for group 1, whereas none of the three deceased patients in group 2 died from GvHD (p<0.005). In the last 18 months, no patients have died from acute GvHD at our center.

In conclusion, DSCs might be an effective treatment of GvHD. The infusion should be prepared in albumin, given as early as possible and in repeated doses. All patients should receive fungal prophylaxis and should be closely monitored for any infectious complications.