![[Visit Client Website]](images/banner.gif)
Conventional steroid treatment for graft versus host disease (GvHD) is effective for a limited number of patients (pts). The use of mesenchymal stromal cells (MSC) as second line of treatment has been reported with promising results. We assessed the safety and efficacy of MSC, in a prospective, multicenter, phase I study (EudraCT 2008-007869-23) for the treatment of steroid resistant grade II-IV GvHD.
Methods
MSC were obtained from bone marrow harvests of third party donors and expanded with platelet lysate. Primary endpoint of the study was safety. Secondary endpoints were response to MSC, overall survival (OS) and transplant-related mortality (TRM). Plasma levels of IL2Ralpha by ELISA were analyzed for enrolled pts.
Results
Between August 2009, and June 2012, 16 children and 31 adults were treated. The median dose of infused MSC was 1.5×106 cells per kg. Enrolled pts presented with acute GvHD in 37 cases, chronic overlap syndrome in 7, and chronic classic GvHD in 3 cases. 15 pts had grade II GvHD, 23 grade III and 9 grade IV, according to NIH criteria. In 17 cases GvHD involved a single organ. Pts were treated with a median of 3 MSC infusions. No significant side effects were registered. 30 patients (63.8%) showed a clinical response. 13 of them (27.6%) had a complete response and 17 (36.1%) a partial response to treatment. 22 over 30 responding pts did not require further lines of immunosuppression after MSC infusion. Response was more likely in pts exhibiting grade II GvHD versus those with severer grading (87.5% vs. 51.6%, p = 0.02) and in pts receiving MSC within 30 days from GvHD onset (75.9% vs. 43.7%, p= 0.05). Median follow up for this cohort is 200 days (range 30-1066). Responders show a significant lower TRM (10.0% vs. 88.2%, p <0.05) and a better OS probability than non responders (23.3% vs. 88.2%, p <0.05). When comparing responders vs non-responders, IL2Ralpha showed a statistically significant difference in terms of fold decrease (p=0.027), corroborating clinical results. Similarly, a significant trend of fold decrease (p=0.058) was observed when comparing responder patients receiving MSC within or after 30 days from GvHD onset, in line with clinical results.
Conclusions
This study confirms that MSC may represent a safe and effective treatment for patients with steroid-refractory GVHD. Plasmatic markers may help in monitoring of clinical response. We suggest to consider the use of MSC as early as possible, after steroid failure.