In conclusion, (1) serum cholinesterase is a simple and reliable marker of acute GVHD and transplant-related complications; and (2) high CHE levels on day +50 predict relapse.
Expression of inducible co-stimulator (ICOS) and B cell lymphoma 6 (Bcl6) increased in the skin, the intestine, the lung, and the liver from CHI3L1-KO splenocyte-treated aGVHD mice.
In multivariate analysis, when adjusted for the European Group for Blood and Marrow Transplantation (EBMT)-Gratwohl score and other prog-nostic factors, there was an independent association between BMI-1 expression and grades 2 to 4 acute graft-versus-host disease (relative risk [RR] = 2.85; 95% confidence interval [CI], 1.3-6.4; P = .011), suggesting that BMI-1 measured prior to allo-SCT can serve as a biomarker for predicting outcome in patients with CP-CML receiving allo-SCT, and may thus contribute to better therapeutic decisions.
This multivariate model also revealed a trend toward less aGVHD in patients receiving a BPI G allele transplant (OR, 0.60; P = .067) and in those receiving a transplant from an HLA-matched donor (OR, 0.57; P = .058).
Finally, experimental induction of GvHD in complement C3-deficient mice confirms the link between Gp96 and complement C3 in the serum and with the severity of the disease.
According to our integrated methodology, transcripts for FOXP3, ICOS, CD52 and CASP1, genes involved in immune alloreactive responses and participating in immune cell interactions, were identified as the most informative biomarkers in allogeneic stem cell transplant recipients experiencing acute graft-versus-host disease.
We were able to monitor the spatiotemporal dynamics of caspase-1 activation and onset of inflammation in individual animals in the context of a systemic bacterial infection, colitis, and acute graft-versus-host disease.
Indeed, Cav-1(-/-)donor T cells caused less severe acute graft-versus-host disease (GVHD) and yielded higher numbers of regulatory T cells (Tregs) compared with controls.
We investigated the expression of aGVHD-related markers (regulated on activation normal T-cell expressed and secretes: RANTES, elafin, REG3α and ST2) and endothelial cell activation markers (soluble vascular cell adhesion molecule: sVCAM-1 and plasminogen activator inhibitor: PAI-1) in patients undergoing allogeneic HSCT.
A previous phase I/II trial demonstrated that CCR5 blockade with maraviroc in the first 30days after allo-HCT resulted in a low incidence of early acute GVHD, primarily in visceral organs, but with no impact on late acute or chronic GVHD.
Recipients carrying the CCR5Delta32 allele developed acute GvHD (grades I-IV) less frequently than did patients lacking the CCR5 deletion mutation (11/35 vs. 76/151, p=0.033).
While acute graft-versus-host-disease (GVHD) is a T cell-mediated disease caused by alloreactive donor T cells, we and others have highlighted that patients who received higher proportion of donor CD4<sup>+</sup> naïve and central memory T cells expressing the chemokine receptor 7 (CCR7) more often developed acute GVHD than those who did not.
Our data suggest that CCR7 inhibition in the early posttransplantation period may represent a feasible new therapeutic approach for acute GVHD attenuation without compromising GVL responses.
Consequently, we examined the ability of cosalane, a recently identified CCR7 small-molecule antagonist, to attenuate aGVHD in mouse HSCT model systems.
In longitudinal clinical studies, receiving a high percentage of allogeneic donor-derived CD4(+) CCR7(+) T cells, which include naïve and central memory subsets have been correlated with increased incidence and severity of acute GVHD.