HA-04. Effects of immunopeptidome diversity on the development of graft failure in patients with acute leukemia
Feruza A. Omarova, Mikhail Yu. Drokov, Ekaterina G. Khamaganova, Natalia N. Popova, Olga S. Starikova, Ulyana V. Maslikova, Zoya V. Konova, Elmira I. Kolgaeva, Ekaterina D. Mikhaltsova, Mariya V. Dovydenko, Olga M. Koroleva, Anna A. Dmitrova, Darya S. Dubnyak, Mobil I. Akhmedov, Vera A. Vasilyeva, Larisa A. Kuzmina, Elena N. Parovichnikova
National Research Center for Hematology, Moscow, Russia
Contact: Dr. Feruza A. Omarova, phone: +7 (977) 992-97-17, e-mail: email@example.com
Graft failure is among the key problems of allogeneic hematopoietic stem cell transplantation (allo-HSCT). This issue is extremely important in case of reduced-intensity conditioning regimens, when a great number of host T-cells still retains in the body. The evolutionary divergence of HLA seems to be interesting, due to its translation to the peptide diversity (including donor ones) which can be presented to residual host T cells. The Grantham distance is a measure for the evolutionary divergence, with its higher levels reflecting the larger number of peptides potentially presented to T-cells via the HLA system. Our aim was to evaluate the impact of immunopeptidome diversity upon development of graft failure in the patients with acute leukemia.
Patients and methods
The present study included 118 patients with acute leukemia, who underwent allo-HSCT at the National Research Center for Hematology (Moscow, Russia). We calculated the Grantham distance for the donor class I HLA determined by the high-resolution HLA-typing using a next-generation sequencing platform. Then we evaluated effects of the Grantham distance on the probability of the post-transplant graft failure. ROC analysis showed that the Grantham distance of >7.4 for HLA-A was associated with higher risk of graft failure. A multivariate analysis was carried out using Cox proportional hazards model, to assess the influence of different factors upon the risks of graft failure. The model included all known factors potentially affecting the graft failure (gender, age, type of conditioning, type of donor, graft source) as well as the Grantham distances for HLA-A.
When analyzing possible effects of different demographic and transplantation-associated factors upon clinical course of the post-transplant period, we have shown that the Grantham distance >7.4 for the donor HLA-A, along with the type of donor, was associated with increased risks of the graft failure (HR, 5; p=0.043).
One may presume that higher diversity of the donor peptide numbers presented to residual host T cells may cause increased risks of immune response against donor cells, thus potentially leading to development of graft failure.
Graft failure, allogeneic hematopoietic stem cell transplantation, HLA system.