PI-03. CMV-specific immune reconstitution in patients after allogeneic hematopoietic stem cell transplantation
Anna A. Dmitrova, Mikhail Yu. Drokov, Larisa A. Kuzmina, Murad S. Vagida, Dmitry O. Kiryukhin, Vera A. Vasilyeva, Natalia N. Popova, Ekaterina D. Mikhaltsova, Maria V. Dovydenko, Olga M. Koroleva, Darya S. Dubnyak, Zoya V. Konova, Mobil I. Akhmedov, Natalia M. Nikiforova, Ulyana V. Maslikova, Olga S. Starikova, Feruza A. Omarova, Elmira I. Kolgaeva, Grigoriy A. Efimov, Elena N. Parovichnikova, Valery G. Savchenko
National Research Center for Hematology, Moscow, Russia
Contacts: Dr. Mikhail Yu. Drokov, e-mail: mdrokov@gmail.com, Dr. Anna A. Dmitrova, e-mail: dr.admitrova@gmail.com
Summary
Introduction
Cytomegalovirus infection (CMV infection) remains one of the most common complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite high frequency of the CMV reactivation in immunocompromised patients, the high costs of antiviral treatment and toxicity as a side effect of therapy also remain a problem. The leading role in the fight against CMV infection belongs to T cells. Reconstitution of the T-cell immunity depends on many factors, for example, conditioning regimen, source of hematopoietic stem cells and the graft-versus-host disease (GvHD) prophylaxis regimen. This study shows the dynamics of quantitative recovery of CMV-specific T-cell immunity in the patients with hematologic malignancies and non-neoplastic hematologic disorders at different time points after allo-HSCT, depending on the GvHD prophylaxis regimen.
Patients and methods
The patients’ characteristics are presented in Table 1. Blood samples were collected on days +30, +90, +180. CMV-specific CD8+ cytotoxic lymphocytes (CMV-CTL) were identified by flow cytometry using fluorochrome-conjugated monoclonal antibodies against CD3, CD8 and CD45 molecules, a viability reagent, and tetramers. The tetramers consisted of MHC monomers class I, associated with one of the immunodominant epitopes at the viral pp65 protein: peptides NLVPMVATV (NLV), TPRVTGGGAM (TPR), RPHERNGFTVL (RPH), presented on the HLA-A * 02 and HLA-B * 07 alleles in complex with streptavidin, labeled with phycoerythin. The total number of leukocytes was assessed using a Sysmex X-2100 blood analyzer. Two-platform method was used to calculate the absolute number of CMV-CTL.
Table 1. Patients’ characteristics
Results
The fastest recovery of CMV-specific T cells was observed when anti-T-lymphocyte globulin (ATG) was included into the additional GVHD prophylaxis. The patients who received T-cell depletion (TCD) and post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis have significantly lower number of CMV-CTL, and these values remained lower until +180 days after allo-HSCT.
Conclusion
T-cell depletion and post-transplant cyclophosphamide included in GvHD prophylaxis regimen have a more “aggressive” effect upon the reconstitution of CMV-specific T cell immunity. Therefore, these groups of patients are candidates for the cell therapy (infusion of CD45RA- lymphocytes, CMV-specific T lymphocytes).
Keywords
Allogeneic hematopoietic stem cell transplantation, cytomegalovirus infection, CMV-specific T-lymphocytes, immunosuppressive therapy, graft-versus-host disease.
