Plasma nitric oxide is associated with the occurrence of moderate to severe acute graft-versus-host disease in haemopoietic stem cell transplant recipients

Abstract

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) has been implicated as one of the mediators of acute graft-versus-host disease (GVHD) but reports on its measurement during haemopoietic stem cell transplantation (HSCT) in human are scarce. The present study was conducted to measure the plasma NO in HSCT recipients in order to delineate its relationships with acute GVHD. DESIGN AND METHODS: Thirty-nine randomly selected patients undergoing HSCT were recruited. Thirty-one patients received allogeneic transplants (ALLO) from HLA-identical siblings (n=20), haploidentical parent (n=1) and matched unrelated donors (n=10). Eight patients received autologous (AUTO) HSCT. Plasma levels of nitrite/nitrate (NO(2)(-)/NO(3)(-)), the end-product of NO, were measured by chemiluminescence and the results were correlated with the occurrence and severity of acute GVHD. RESULTS: Baseline NO(2)(-)/NO(3)(-) levels before HSCT were similar in the ALLO and AUTO patients (17.4 vs 21.1 microL, p>0.05). Significant increases in plasma NO(2)(-)/NO(3)(-) (> 2 times the baseline level) were found in all 13 patients with acute GVHD > or = grade 2, in 15 out of 18 patients with acute GVHD grade < or = 1 and 3 out of 8 patients receiving autologous HSCT. The increase in NO(2)(-)/NO(3)(-) among the three groups of patients was significantly different (135.5 vs 56.3 vs 36.6 micromol/L, p < 0.001). The average NO production, calculated as the area under the curve, was also significantly differently among the three groups of patients (44.5 vs 30.0 vs 23.8 micromol/L, p < 0.001). INTERPRETATION AND CONCLUSIONS: Plasma NO in HSCT recipients is quantitatively associated with the occurrence of acute GVHD and its role remains to be determined.