MONITORING SOLUBLE INTERLEUKIN-2 RECEPTOR LEVELS IN RELATED AND UNRELATED DONOR ALLOGENEIC BONE-MARROW TRANSPLANTATION

Acute graft-versus-host disease (GVHD) is effected by donor T lymphocy tes which have been stimulated by host antigens. Activated donor T lym phocytes express interleukin-2 receptor (IL-2R), which is comprised of three submits (alpha, beta, gamma). During activation, the alpha IL-2 R submit (CD25) is shed from the receptor complex and can be measured in the circulation. Soluble IL-2R alpha (sIL-2R) levels are increased in states of immune activation including GVHD, and could theoretically be used as a guide to therapy. Since IL-2R alpha expression is an ear ly marker of T cell activation, we investigated: (1) if an increase in sIL-2R is specific for acute GVHD; and (2) if serial sIL-2R levels ca n identify patients with early GVHD, prior to the onset of clinical ti ssue damage (effector function). Weekly sIL-2R levels were monitored i n 36 patients undergoing matched related (n = 23) or matched unrelated (n = 13) allogeneic bone marrow transplantation (BMT). There was no s ignificant difference in sIL-2R levels between matched related and mat ched unrelated recipients. Patients with acute GVHD (n = 19, 53%) demo nstrated higher sIL-2R levels, than those without during weeks 2 and 3 post-BMT (P = 0.02 and 0.04, Mann-Whitney U test, two-tailed). In pat ients with acute GVHD, the rise in sIL-2R preceded the clinical signs of GVHD (16/19 patients). However, patients with sepsis demonstrated a trend towards higher sIL-2R levels at week 1 and significantly greate r levels by week 4 (P = 0.02). Furthermore, patients with veno-occlusi ve disease (VOD) (25%) also had significantly higher sIL-2R levels at week 2 (P = 0.03). We conclude that although sIL-2R levels increase in patients with acute GVHD, similar increases are seen in patients with VOD and/or sepsis and therefore, as a single biochemical marker, we f ind that serial measurements of sIL-2R lacks sufficient specificity to guide GVHD therapy.