Multipotent Mesenchymal Stromal Cells as Graft-Versus-Host Disease Prophylaxis: a Prospective Randomised Clinical Trial

Abstract 1256

Acute and chronic graft-versus-host disease (GvHD) develops in more than 50% patients after hemopoietic stem cell transplantation (HSCT) and remains one of main causes of mortality. That's why it is still very important to find new methods of GvHD prophylaxis and treatment. There is a wellknown algorithm of GvHD treatment with glucocorticoids as first line and there are many other options in the treatment of steroid-resistant GvHD, including multipotent mesenchymal stromal cells (MMSC). The efficacy of MMSC in the treatment of steroid-resistant GvHD was reported to be 71–94% (Le Blanc et al., Lancet, 2008; Kebriaei et al., Biol Blood Marrow Transplant, 2009). There are few data on using MMSC as GvHD prophylaxis. So we designed a trial based on a random patient allocation in two groups: receiving standard GvHD prophylaxis (cyclosporine A + methotrexate, cyclosporine A + methotrexate + prednisolon, or cyclosporine A +methotrexate+ mycophenolate mofetil) and receiving MMSC in addition to the standard GvHD prophylaxis. The goal of the study was to investigate the efficacy and safety of MMSC administration as graft-versus-host disease prophylaxis. MMSC were derived from the bone marrow of hemopoietic stem cells donors and cultured in alpha-MEM with 4% human platelet lysate derived from peripheral blood of the same donors. The bone marrow sample was aspirated at the day of HSCT. The trial was approved by local ethic committee and started in October, 2008. Currently 22 patients with stem cell transplantation from related donors are randomised. 10 patients received standard GvHD prophylaxis and 12 received MMSC in addition. 5 patients received fresh cultivated MMSCs while others – MMSCs after freezing and thawing procedures, carried out in standard conditions. Patients characteristics are presented in the Table 1.

MMSCs were administered at the time of blood counts recovery. The dose of MMSC was 0.9–1.25×10⁶/kg. The median day of administration was + 30 day after HSCT (25-54 dd). Most of the patients had fever and chills after MMSC administration. There were no other complications.

The clear difference in acute GvHD development was observed in two groups. In standard prophylaxis group acute GvHD II-IV developed in 50% patients, in MMSC group no acute GvHD II-IV occurred (p=0,009). Two patients in the second group had acute GvHD I developed before MMSC administration. The regression of symptoms was observed after MMSC injection. Chronic GvHD was diagnosed in 40% patients in the first group and in 16.7% patients in the second group. There was no difference in disease recurrence rate and graft rejection rate. More infectious complications occurred in patients from MMSC prophylaxis group, mostly of viral origin. There were no lethal infections in this group. The overall mortality was similar in both groups (20% compared to 8.4% in MMSC group).

The results of our small study clearly demonstrate the efficacy and safety of MMSC administration as graft-versus-host disease prophylaxis. We intend to continue the study and we incorporated the MMSC as treatment option in steroid-resistant GvHD.

No relevant conflicts of interest to declare.