Page 181 - Haematologica-April 2018

Tocilizumab for the prevention of acute GvHD
A
B
Figure 5. Reconstitution of major lymphocyte subsets in patients who received tocilizumab for GvHD prophylaxis. (A,B). The absolute number of cells per mm3 (i.e., microliter) is shown in panel A, and the percentage of the gated cells is shown in panel B. Data are shown for individual patients together with the median and 25th and 75th quartiles (red bars). Gray shading represents the upper and lower range expected for healthy control subjects. Samples were obtained at one month (n=33), three months (n=29), six months (n=22), and 12 months (n=13). Lymphocytes were gated on total CD45+ white blood cells, and all other subsets were gated on lym- phocytes. NK: natural killer.
immunoassay used to detect sIL-6R levels captures free sIL-6R, IL-6R bound to IL-6, and IL-6R bound to Toc.44 Therefore, we cannot distinguish the composition of the sIL-6R complex, but it is likely that a significant compo- nent is attributable to the binding of Toc to IL-6R, given that a prior study showed that Toc can be detected for up to one month in allogeneic stem cell transplant recipi- ents.18 This would therefore also explain the high IL-6 lev- els in these patients, as free IL-6 may have been precluded
from binding to the Toc/sIL-6R complex. The fact that IL- 6 levels were higher in patients treated with MA versus RIC, however, suggests that the conditioning regimen itself also contributed to the increase in IL-6 levels. Notably, we did not observe meaningful increases in any of the other cytokines that we examined (i.e., IL-2, IL-4, IL-10, TNF-α, IFN-g and IL-17) in control or Toc-treated patients, providing evidence that dysregulation of IL-6 is an important early event post-transplantation. Toc had no
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