Incipient Release of Leukocytes After Allogeneic Hematopoietic Cell Transplantation Is Indicated by Increasing Serum Levels of Uric Acid Before Detection of First Leukocytes

Abstract 4701

Uric acid serves as an endogenous danger signal to the immune system upon the release from dying cells activating both innate and adaptive immunity. Multiple cytokines and danger signals are released into the blood modulating cellular and humoral immune responses during haematopoietic cell transplantation (HCT). Here, we investigated serum levels of uric acid during haematopoietic regeneration after allogeneic HCT to evaluate whether uric acid can be used as marker for hematopoietic engraftment indicating immunologic activity below the detection limit of differential blood counts (50/μ l). Differential blood counts and serum levels of uric acid, creatinine and urea were retrospectively analyzed in 47 consecutive patients (22 men and 25 women, median age 48 years, range 19 to 73 years) during 50 allogeneic HCT (three patients received a second transplantation due to recurrent disease). Serum levels of uric acid, creatinine and peripheral blood counts were determined daily. All patients received allopurinol for 5 days from the beginning of the conditioning which was discontinued afterwards. The mean nadir in uric acid levels was observed 13.4 days after the last dose of allopurinol (range 2 to 32 days) and 9.1 days after transplantation (range 2 to 21 days) irrespective of the conditioning regimen used. In all patients a significant decrease of uric acid serum levels after the transplantation was observed (Student's t-test, p < 0.001). A re-increase of uric acid was observed 1 to 10 days (mean 4.1 days, SD 2.4) before detection of white blood cells (leukocytes > 50/μ L) in 35 out of 50 transplantations (70%, group 1). In three cases (6%), the increase of uric acid levels was observed concomitantly with increasing leukocytes (group 2). In the remaining 12 cases, this elevation was only observed later (1 to 6 days after re-increase of leukocytes, mean 2.8 days, SD 1.5, group 3). The difference between group 1 and 3 was statistically significant (Student's t-test, p < 0.001). No correlation with patient age, conditioning regimen, HLA compatibility or additional medications could be observed. Therefore, a re-increase of uric acid can be indicative for incipient haematopoietic engraftment after allogeneic HCT and may serve as indicator for consumption of the ealiest differentiated cells in peripheral blood even before leukocytes can be detected.