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.

Keywords: Acute leukemia; Allogeneic hematopoietic stem cell transplantation; Graft-versus-host disease; Graft-versus-leukemia effect; Invariant NKT cells; Myeloid-derived suppressor cells.

Fig. 1

Cumulative incidence of grade III–IV acute GVHD accoring to the combinations of frequency of invariant natural killer cells (iNKT) and monocytic myeloid-derived suppressor cell population (M-MDSC). Black line, lower iNKT (≤ 0.027%) + lower M-MDSC (≤ 0.27%), n=19; Red line, lower iNKT (≤ 0.027%) + higher M-MDSC (> 0.27%), n=20; Green line, higher iNKT (> 0.027%) + lower M-MDSC (≤ 0.27%), n=42; Blue line, higher iNKT (> 0.027%) + lower M-MDSC (> 0.27%), n=36.

Fig. 2

Major outcomes accoring to the combinations of frequency of invariant natural killer cells (iNKT) and monocytic myeloid-derived suppressor cell population (M-MDSC). Black line, lower iNKT (≤ 0.027%) + lower M-MDSC (≤ 0.27%), n=19; Red line, lower iNKT (≤ 0.027%) + higher M-MDSC (> 0.27%), n=20; Green line, higher iNKT (> 0.027%) + lower M-MDSC (≤ 0.27%), n=42; Blue line, higher iNKT (> 0.027%) + lower M-MDSC (> 0.27%), n=36. (A) Overall survival, (B) disease-free survival, (C) cumulative incidence of relaspse, and (D) cumualtive incidence of transplant-related mortality (TRM).