Soluble interleukin-2 receptor concentration as a biochemical indicator for acute graft-versus-host disease after allogeneic bone marrow transplantation

When interleukin-2 (IL-2) binds to the IL-2 receptor (IL2-R) on activated T cells, a soluble portion of the receptor (sIL2-R) is released. After allog eneic bone marrow transplantation (BMT), the serum concentration of sIL2-R may, therefore, be a useful surrogate marker for T cell activation that res ults in acute graft-versus-host disease (aGVHD). To determine if the sIL2-R concentration is a useful marker to help establish a diagnosis of aGVHD, s erial sIL2-R concentrations were measured weekly for 4 weeks in 43 patients after allogeneic BMT. Grafts were from HLA-matched siblings (n = 33), 5/6 HLA-matched siblings (n = 3) or matched unrelated donors (n = 7). GVHD prop hylaxis included cyclosporine A (CSA)/methotrexate (MTX) (n = 25), solumedr ol/CSA (n = 15), or T cell depletion (n = 3). Twenty-three patients develop ed aGVHD (Grade I, 7; Grade II, 12; Grade III, 4) a median of 28 days after transplant. There was a significant association between a clinical diagnos is of aGVHD and an increase in the sIL2-R concentration (p < 0.001). The me an percent increase (I-SE) over baseline for patients with a clinical diagn osis of aGVHD was 294% (+/- 57%) by week 2 (n = 12), 431% (+/- 116%) by wee k 3 (n = 14), and 650% (+/- 315%) by week 4 (n = 9) after BMT. For each 100 % increase over baseline, the likelihood of having aGVHD increased by 18%. Six of 20 patients without aGVHD became critically ill and exhibited marked increases in sIL2-R concentrations, similar to patients with a clinical di agnosis of aGVHD who never became critically ill. Fourteen patients without aGVHD who did not become critically ill exhibited negligible increases of sIL2-R in 2- to 4-week period after BMT. These data suggest that serial mea surements sIL2-R concentration are helpful in establishing the diagnosis of aGVHD, but are not useful in the most acutely ill patients.