Reconstitution of CD8+ T-memory cells after different GVHD prophylaxis regimens in acute leukemia patients after allogeneic stem cells transplantation
Natalia N. Popova, Mikhail Y. Drokov, Yulia O. Davydova, Nikolay M. Kapranov, Uliyana V. Maslikova, Ekaterina D. Mikhaltsova, Vera A. Vasilyeva, Olga M. Koroleva, Zoya V. Konova, Anna A. Dmitrova, Maria V. Dovydenko, Olga S. Starikova, Darya S. Dubnyak, Denis V. Kamelskikh, Irina V. Galtseva, Tatyana V. Gaponova, Michael A. Maschan, Larisa A. Kuzmina, Elena N. Parovichnikova, Valery G. Savchenko
National Medical Research Center for Hematology, Moscow, Russia
Contact: Dr. Mikhail Yu. Drokov
Acute graft-versus-host disease (aGVHD) is the main problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT) effecting patients’ morbidity and mortality.
Alternative aGVHD prophylaxis regimens are based on graft manipulated procedure (TCR αβ-depletion) or posttransplant cyclophosphamide (PT-CY) now available for recipients of mismatched or haploidentical hematopoietic stem cells. However it’s considered that applying of these approaches is accompanying with prolonged immune recovery. But that should be established further. Our aim was to evaluate an impact of different aGVHD prophylaxis regimens on CD8+ T-memory cells reconstitution after allo-HSCT in acute leukemia patients.
Patients and methods
The study comprised 65 leukemia patients who underwent allo-HSCT in National Research Center for Hematology, Russia. All patients were subdivided in 3 groups due to aGVHD prophylaxis regimen. 32 patients (a median age of 33, range 20 to 61 y.o.) received Antithymocyte Globulin (ATG) based immunosuppressive regimen with Cyclosporin A and Mycophenolate Mofetil, 18 patients (a median age of 36, range 23 to 58 y.o.) received ATG with PT-CY on day +3,+4, and 15 patients (a median age of 22, range 17 to 57 y.o.) underwent TCR αβ-depleted transplant. ATG-based regimen was applied in case of matched related and matched unrelated donors. The alternative approaches were used in case of mismatched donors: ATG+PT-CY was administered in patients who underwent allo-HSCT from unrelated mismatched donors or related haploidentical donors, and TCRαβ-depletion was carried out in haploidentical transplants. Acute GVHD with grade II-IV was diagnosed in 13 (40.6%) patients after ATG-based prophylaxis, in 3 (16,7%) – after ATG+PT-CY, in 3 (20%) – after TCR αβ-depletion. Samples of peripheral blood were collected on day +30, +60, +90 and +180 after allo-HSCT in EDTA-tubes. Flow cytometry analysis was performed on BD FACS Canto II (Becton Dickinson, USA) to define CD8+ T-memory subsets: T-naive and T-stem cell memory (Tnv+Tscm) – CD45R0-CCR7+CD28+; T-central memory (Tcm) – CD45R0+CCR7+CD28+; T-transitional memory (Ttm) – CD45R0+CCR7-CD28+; T-effector memory (Tem) – CD45R0+CCR7-CD28-; T-terminal effector (Tte) – CD45R0-CCR7-CD28-. Kruskal-Wallis test was used to determine nonparametric data analysis for 3 independent groups. A p-value less than 0.05 was considered as significant. All data analysis was conducted utilizing SPSS ver. 23. (IBM, Chicago, Ill., USA).
Absolute number of CD8+ Tnv+scm, Tcm, Ttm, Tem, Tte on day +30, +60, +90, +180 is summarized in the Table 1.
Table 1. Absolute number of different CD8+ T-memory cells after allo-HSCT, depending on aGVHD prophylaxis regimens
The lower number of CD8+ Tnv+scm and Tcm after alternative regimens comparing ATG-based prophylaxis in early period (on day +30, +60, +90) after allo-HSCT might reflect severe immunoablation in case of allo-HSCT from mismatched and haploidentical donors. This factor might be crucial in terms of restraining potential aGVHD onset. However, lower number of effector cells (Ttm, Tem, Tte) after TCR αβ-depletion and ATG+PT-CY on day +180, as compared to ATG-based immunosuppression might indicate prolonged immune recovery in mismatched or haploidentical recipients. It’s important to note that the lowest number of all T-cell types after TCR αβ-depletion points to delayed immune recovery after this approach comparing to ATG+PT-CY. That might require providing of different supportive strategies in patients after TCR αβ-depletion, in order to boost their immune recovery.
No relevant conflicts of interest to declare.
T-memory cells, immune reconstitution, allogeneic stem cell transplantation, GVHD prophylaxis regimens.