Children and Adults with Steroid-Refractory Acute Graft-Versus-Host Disease Respond to Treatment with the Mesenchymal Stroma Cell Preparation “MSC-FFM”: Treatment Results for 92 Consecutive Patients

Introduction: Since the seminal paper of LeBlanc in 2008, despite several negative studies, the scientific community has retained optimism with respect to the usefulness of mesenchymal stroma cells (MSCs) in refractory acute graft-versus-host disease (GvHD). A prevailing theme of past studies was that, while pediatric GvHD responded to MSCs, adult GvHD did not. As reported, we developed proprietary protocols GMP-quality MSC production from bone marrow (BM) mononuclear cells expanded in platelet lysate-enriched media. Patients and Methods: We present treatment data with MSC-FFM for 61 children/adolescents and 31 adults with either “only” steroid-refractory (SR) GvHD (27%) or GvHD which had additionally proven refractory to up to five additional lines of therapy (MR-GvHD) (73%). Pediatric patients tended to have more MR-GvHD than adults. Patients from 23 centers in 6 countries were included. Most patients had severe GvHD (37% °III, 59% °IV, Glucksberg scale). 31 patients (34%) were female,61 male (66%). 69 have a malignant disease (75%), and 23 a non-malignant (25%) disease as indication for transplantation. Donors were MSD (n=21, 23%), MUD (n=56, 61%), haploidentical (n=14, 15%), and 1 MMUD (1%). Patients received myeloablative conditioning with TBI-, Treosulfan-, Busulfan- and Fludarabine-based regimen, with serotherapy, mostly ATG. 89% of patients had had immunosuppression for GvHD prophylaxis, 13% CSA alone, 49% CSA+MTX or MMF; or others (n=15, 16%). Median onset of aGvHD was at 40 days (range: 6-280 d), another 28 days (range: 5-380) until the first infusion of MSC-FFM. Recommended dose and interval is 4 weekly doses of 1-2M MSC/kg body weight; the average patient received only 3 doses, the interval approximately staggered as recommended, with a median dose of 1.4M MSC/kg. Any reduction in GvHD activity by at least one full grade was classified as a partial (PR), absence of any degree of GvHD as a complete response (CR). Results: Day-28 response rates were 84%/25%/59% overall (OR)/CR/PR for children and 80%/35%/45% for adults resulting in a day-28 response rate for the entire cohort: 82%/28%/54%). At last follow-up (LFU) many of the pediatric responders had continued to improve from partial to complete response to response rates of 84%/59%/25% OR/CR/PR, in adults responses were largely unchanged (77%/35%/42%; LFU for the entire cohort: 81%/51%/30%). GvHD °III and °IV were equally likely to respond or resolve. Looking at response rates of SR- vs. MR-GvHD