Editors' ChoiceGraft-Versus-Host Disease

Putting Out the Fire

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Science Translational Medicine  14 Dec 2011:
Vol. 3, Issue 113, pp. 113ec203
DOI: 10.1126/scitranslmed.3003554

Chronic graft-versus-host disease (GVHD)—which occurs in the majority of patients who receive hematopoietic stem cell transplants from other people, generally to treat diseases such as leukemia—causes considerable morbidity and mortality. In this smoldering systemic inflammatory disorder, immune cells from the donor attack the host. It is thought that regulatory T cells (Treg cells), which normally function to suppress autoreactive immune cells, are impaired in chronic GVHD. Systemic glucorticoids, which are steroid hormones that tamp down the immune system, have been used with limited efficacy to treat chronic GVHD but are associated with long-term toxicity; second-line therapy has remained elusive.

However, recently Koreth et al. reported a new strategy to put an end to the flame of GVHD. These researchers tested whether interleukin-2, a cytokine that is important for Treg cell function, might ameliorate the symptoms of chronic GVHD. In this observational study, patients with chronic GVHD who were refractory to glucocorticoids received low daily doses of interleukin-2 for 8 weeks.

Of the 23 of 29 enrolled patients who could be evaluated for their response, none had progression of their GVHD or relapse of their hematologic malignancies. Twelve of the 23 patients had major improvements in their GVHD-related symptoms. In addition, the number of Treg cells was preferentially increased relative to conventional T cells (Tcon cells) to a peak median value of over eight times the baseline value. The Treg:Tcon ratio increased by a median of five times the baseline value. These Treg cells could inhibit proliferation of Tcon cells ex vivo. More importantly, the effects of this treatment were sustained in patients who received interleukin-2 over an extended period of time, allowing for a large reduction in the glucocorticoid dose. If this approach is effective in a larger subset of patients with chronic GVHD, interleukin-2 could represent the new standard for treating this dangerous disorder.

J. Koreth et al., Interleukin-2 and regulatory T cells in graft-versus-host disease. N. Engl. J. Med. 365, 2055–2066 (2011). [PubMed]

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