Bone marrow or stem cell transplantation
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially curative in several hematological and immunological disorders. It carries the risk graft-versus-host disease (GvHD). Risk factors for GvHD are established and include recipient age, female-to-male transplantation, and Human Leukocyte Antigen (HLA) and Cytomegalovirus (CMV) immunity mismatch. We have developed an assay to determine glucocorticoid (GC) responsiveness (GCR) in peripheral leukocytes. Using this assay, we found that preoperative GCR relates to postoperative recovery in surgical patients. In this study we applied this assay to CD34-depleted HSCT grafts, to investigate if GCR can predict GvHD grade ≥2 in allo-HSCT recipients.
Material and methods
Graft cells, harvested for transplantation to 24 patients (mean age 53 (SD ±13), 8:16 female:male) with hematological malignancies, were incubated overnight in 108 M, 106 M Dexamethasone (DEX) or DEX-free medium. Relative up- and down-regulation for five GC regulated genes was determined by RTq-PCR. GvHD grade was determined by clinical review. Ten patients developed acute GvHD grade 2-3.
Reduced DEX-induced down-regulation of the GC receptor alpha (GR-alpha) and HLA-DR genes was found in grafts for recipients developing GvHD grade ≥2 (p < 0.05). Added to the risk factors for acute GvHD (above) logarithmized relative expression levels of GR-alpha and HLA-DR, at either DEX concentration, improved prediction of GvHD grade ≥2, in logistic regression models (p < 0.001).
We conclude that measuring graft GC responsiveness by RTq-PCR of DEX-induced downregulation of GC regulated genes GR-alpha and HLA-DR may add value in the prediction of risk of acute GvHD in adult allo-HSCT recipients.