Analysis of results of acute graft-versus-host disease prophylaxis with donor multipotent mesenchymal stromal cells in patients with hemoblastoses after allogeneic bone marrow transplantation

Abstract

Allogeneic bone marrow transplantation (allo-BMT) is currently the only way to cure many hematoproliferative disorders. However, allo-BMT use is limited by severe complications, the foremost being graft-versus-host disease (GVHD). Due to the lack of efficiency of the existing methods of GVHD prophylaxis, new methods are being actively explored, including the use of donors' multipotent mesenchymal stromal cells (MMSC). In this work, we analyzed the results of acute GVHD (aGVHD) prophylaxis by means of MMSC injections after allo-BMT in patients with hematological malignancies. The study included 77 patients. They were randomized into two groups - those receiving standard prophylaxis of aGVHD and those who were additionally infused with MMSC derived from the bone marrow of hematopoietic stem cell donors. We found that the infusion of MMSC halves the incidence of aGVHD and increases the overall survival of patients. Four of 39 MMSC samples were ineffective for preventing aGVHD. Analysis of individual donor characteristics (gender, age, body mass index) and the MMSC properties of these donors (growth parameters, level of expression of 30 genes involved in proliferation, differentiation, and immunomodulation) revealed no significant difference between the MMSC that were effective or ineffective for preventing aGVHD. We used multiple logistic regression to establish a combination of features that characterize the most suitable MMSC samples for the prevention of aGVHD. A model predicting MMSC sample success for aGVHD prophylaxis was constructed. Significant model parameters were increased relative expression of the FGFR1 gene in combination with reduced expression levels of the PPARG and IGF1 genes. Depending on the chosen margin for probability of successful application of MMSC, this model correctly predicts the outcome of the use of MMSC in 82-94% of cases. The proposed model of prospective evaluation of the effectiveness of MMSC samples will enable prevention of the development of aGVHD in the maximal number of patients.

Hematopoietic stem cells as a tool for the treatment of glioblastoma multiforme

“…A crucial stage in treatment of oncohematologic diseases and certain other cancer types is radiation and high-dosage chemotherapy. By eliminating hematopoietic cells these strategies destroy their local microsurroundings in bone marrow, while the transplanted stem cells will find their way to the damaged area, populate and remodel it by creating new conditions of local microenvironment (19,20). …”

Analysis of multipotent mesenchymal stromal cells used for acute graft‐versus‐host disease prophylaxis

“…The prediction of the success of an MSC sample for aGvHD prophylaxis may not be solely based on the combination of IDO1, CFH, and IGF1 REL in this model. Another combination of parameters was revealed as prognostic while attempting to explain the inefficiency of aGvHD prophylaxis in patients who underwent allo‐HCT and were not in remission . In this model, a decrease in the expression level of the receptor for the basic fibroblast growth factor (FGFR1) combined with an increase in the expression levels of differentiation‐related (PPARG) and aging‐related (IGF1) genes indicated that MSCs that failed to prevent aGvHD primarily consisted of mature cells.…”

Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease—a meta-analysis

“…The search strategy is detailed in Table S1 (see Additional file, pp. [29][30]. Only full-text clinical studies published in English were included.…”

“…For most studies, a single dose of MSC was administered on the same day than HSCT while in 4 studies, a second dose of MSC was also administered on day + 2 [25], + 14 [26,27] or + 21 [28] after HSCT. In two studies, the single administration of MSC was carried out after HSCT, on day + 28 (19-54) [29] or after more than 4 months after transplantation [30]. Any of the studies included to evaluate the effect of MSC infusion for the prophylaxis of GvHD showed low risk for the six domains of RoBANS ( Figure S1, see Additional file, pp.…”