Predictive Role of Circulating Immune Cell Subtypes Early after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia

Abstract

Background and Objectives Cells of innate immunity normally recover in the first weeks to months after allogenenic hematopoietic stem cell transplantation (allo-HSCT). Their relevance in terms of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect is largely unknown. The predictive role of early recovery in the immune cells on acute GVHD and GVL effect after allo-HSCT was investigated in patients with acute leukemia who achieved the first complete remission. Methods Peripheral blood samples were taken at the median of 14 days (range, 12~29 days) after allo-HSCT. A cohort including 119 samples and characteristics of patients were analyzed. Immune cell populations were identified by flow cytometry. Results The median age was 49.0 years (range, 21~69) at transplantation. Univariate analysis showed that age less than 40 years old, lower frequencies of CD8 + T cells, invariant natural killer T (iNKT) cells, monocytic myeloid derived suppressor cells (M-MDSCs) and higher frequency of immature MDSCs were associated with occurrence of grade III–IV acute GVHD. Multivariate analyses showed that iNKT cells (hazard ratio (HR), 0.453, 95% CI, 0.091~0.844, p=0.024) and M-MDSCs (HR, 0.271, 95% CI, 0.078~0.937, p=0.039) were independent factors. Combination of higher frequencies of both cell subsets was associated with lower incidence of grade III–IV acute GVHD, whereas patients with lower frequency of iNKT cells and higher frequency of M-MDSCs showed significant higher probability of relapse. Conclusions iNKT cells and M-MDSCs could be relevant cell biomarkers for predicting acute GVHD and/or relapse in acute leukemia patients treated with allo-HSCT.

NK cell predicts the severity of acute graft-versus-host disease in patients after allogeneic stem cell transplantation using antithymocyte globulin (ATG) in pretreatment scheme

“…The benefit from NK cell may be attributed to its introduction of controllable GVHD together with an optimal degree of GVL effect, In a separate study, it was shown that serum IFN-γ increased along with the expansion of NKT-like cells in GVHD patients, and patients benefitted through treatment with basiliximab (anti-CD25 antibody) and etanercept (anti- IFN-γ antibody) [3]. Kim et al revealed that lower frequencies of iNKT cells (invariant NKT cells) were associated with higher GVHD incidence [19]. The study of NK cells showed similar suppression function on GVHD [20].…”

Reconstitution of T Cell Subsets Following Allogeneic Hematopoietic Cell Transplantation

“…Similar to MAIT cells, they are capable of secreting large amounts of cytokines upon activation in TCR-dependent and TCR-independent manners [89]. High numbers of iNKT cells in the graft and early after allo-HCT are associated with protection against GvHD [101][102][103][104][105][106] and relapse [103,106,107] and seems to be correlated with improved overall survival [103]. Therefore, using this T cell population as immunotherapy and increasing the iNKT cell numbers after allo-HCT has gained attention in recent years.…”

Myeloid-Derived Suppressor Cells in the Context of Allogeneic Hematopoietic Stem Cell Transplantation

“…In humans, MDSCs have been related to worse outcomes in hematological malignancies (60,61); therefore, MDSCs were suspected to be involved in relapses after allo-HSCT. However, in the allo-HSCT setting, only a few prospective studies have reported a significantly higher probability of relapse in patients with higher M-MDSC frequencies than other patients, in the 30 days following allo-HSCT (52,53). Other studies suggested that MDSCs preserved the GVT effect (26,56).…”