2022-01 Nikolay Tsvetkov
Evaluation of the effect of the drug luspatercept on the bone marrow microenvironment in patients with myelodysplastic syndrome in the context of allogeneic bone transplantation in order to search for potential methods of preventing graft failure and poor graft function
735 636 rubles
Myelodysplastic syndrome (MDS) is a malignant disease of the blood and bone marrow with an unfavorable prognosis, since there are no drugs that can cure it. Currently, the only radical method of treating MDS is allogeneic hematopoietic stem cell transplantation (allo-HSCT).
However, there are unresolved problems associated with poor graft function, graft failure and relapse after allo-HSCT, which significantly worsen the results of treatment of patients. It has been shown that these problems are associated with the bone marrow microenvironment in MDS, in which mesenchymal stromal cells (MSCs) are actively involved in maintaining the vital activity of hematopoietic stem cells (HSCs). The microenvironment in MDS not only contributes to a decrease in blood counts, but can also negatively affect the engraftment of normal allogeneic HSCs.
The drug luspatercept is a recombinant protein that is able to bind to TGF-β molecules and restore the late stage of erythropoiesis in MDS. It was also shown that treatment with luspatercept restored the normal function of MSCs in MDS. MSCs play a key role in the development of poor graft function and graft failure after allo-HSCT in MDS. The therapeutic effect on the bone marrow stroma has already been demonstrated for luspatercept, although no evidence of its effectiveness in the context of allo-HSCT has yet been found.
In our study, we plan to obtain experimental data on the therapeutic activity of luspatercept on MSCs both at the time before allo-HSCT and then during the early period after transplantation. The obtained data can be used in the future to solve the problem of graft failure and the development of relapse after allo-HSCT.