Abstract
Abstract 4178
We have reported that evaluating the activation markers and homing molecules not only on T-cells but also on monocytes, combined with cytokine profiling, provides useful information for management of patients with prolonged GVHD (the 53th ASH). In the cases both T-cells and monocytes were highly activated as shown in Fig.1A, we have shown that steroid response was quite effective. When only T-cells were activated, administration of calcineurin inhibitors (CI) alone was sufficient to control the disease. However steroid refractory or steroid dependent patients are presented at a uniform rate. We have employed low dose MTX for these patients, which is widely used in autoimmune diseases because of its anti-inflammatory activity. In this report, we showed the transitional change of both T-cell and monocyte activation status in patients with prolonged GVHD after initiating immunosuppressive agents, especially in some steroid dependent cases given weekly low dose MTX.
We evaluated activation markers and homing molecules not only on T-cells but also on monocytes in peripheral blood obtained from 32 childhood patients (more than 700 samples at various time points) receiving hematopoietic stem cell transplantation (HSCT) by multicolor flowcytometry. The following markers were used: CD69, CD25, and HLA-DR for T cell activation, CCR4, CCR5, CXCR3, CCR9, and CLA for homing markers. Inflammatory monocytes were defined as CD14dimCD16+ cells or CD14+CD163+ cells. In addition we combined the data of cytokine profiles secreted mainly by T cells such as soluble interleukin 2 receptor (sIL-2R), or monocytes such as neopterin, or both such as tumor necrosis factor-ƒ¿ (TNF-ƒ¿), soluble TNF-ƒ¿RI, and soluble TNF-ƒ¿RII.
Representative pattern of combined T-cells and monocytes activation was shown in Fig.1A. After initiating sufficient dose of steroid, both T-cells and monocytes were fully suppressed as shown in Fig.1B. When steroid was tapered just below the maintenance dose, both CD4+CCR5+ CXCR3+ and CD8+CCR5+ inflammatory T-cells were gradually increased without hypercytokinemia, and also increased frequency of CD4+CD45RO+ T-cell subpopulation was observed without any sign of GVHD exacerbations as shown in Fig.1C. In these condition, additional steroid or extra immunosuppressive drug such as weekly low dose MTX could gradually recover to fully suppressed state as shown in Fig.1D.
Evaluating prolonged GVHD by both T-cells and monocytes, combined with cytokine profiling, could lead to early detection of immunological changes before GVHD symptom develops. We can choose appropriate drug use such as weekly low dose MTX for steroid-sparing.
No relevant conflicts of interest to declare.
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