Int J Stem Cells.  2019 Mar;12(1):73-83. 10.15283/ijsc18094.

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

• Kim TW
• Park SS
• Lim JY
• Min GJ
• Park S
• Jeon YW
• Yahng SA
• Shin SH
• Lee SE
• Yoon JH
• Cho BS
• Eom KS
• Lee S
• Kim HJ
• Min CK

• KMID: 2447226
• DOI: http://doi.org/10.15283/ijsc18094

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.

Keyword

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

MeSH Terms

Biomarkers
Cohort Studies
Flow Cytometry
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation*
Hematopoietic Stem Cells*
Humans
Immunity, Innate
Incidence
Leukemia*
Multivariate Analysis
Natural Killer T-Cells
Recurrence
T-Lymphocytes
Biomarkers

Figure

• 

  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).

Reference

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