ABSTRACT
Vitamin D, a hormone involved in bone and calcium homeostasis, has been shown to have potent immunomodulatory effects. We performed a retrospective cohort analysis to evaluate whether monohydroxyvitamin D levels before allogeneic hematopoietic SCT (HSCT) correlate with the risk of GVHD. Fifty-three patients who underwent myeloablative HSCT were studied. Vitamin D levels were measured in serum samples obtained before HSCT. The median 25-hydroxyvitamin vitamin D level was 21.9 ng/mL (7.8-45.7). The cumulative incidence (CI) of grades II-IV acute GVHD at 100 days was 53.1% in patients with vitamin D<25, versus 33.3% in patients with vitamin D ≥ 25 ng/mL (P=0.13). The CI of chronic GVHD (cGVHD) at 2 years in patients with vitamin D<25 was 63.8%, compared with 23.8% in patients with vitamin D ≥ 25 ng/mL (P=0.009). Similarly, the 2 year CI of extensive cGVHD was significantly greater in patients with vitamin D<25 compared with those with vitamin D ≥ 25 ng/mL (54.5% versus 14.3%, P=0.005). In a multivariable competing risk model, low pre-transplant vitamin D levels remained a significant factor associated with cGVHD (hazard ratio=5.26, P=0.02). Our results demonstrate that vitamin D deficiency before HSCT is associated with an increased risk of cGVHD.
Subject(s)
Graft vs Host Disease , Stem Cell Transplantation , Vitamin D/analogs & derivatives , Acute Disease , Adolescent , Adult , Chronic Disease , Female , Graft vs Host Disease/blood , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Transplantation, Homologous , Vitamin D/bloodSubject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Hepatic Veno-Occlusive Disease , Adolescent , Adult , Aminoglycosides/adverse effects , Aminoglycosides/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Child , Child, Preschool , Female , Gemtuzumab , Hepatic Veno-Occlusive Disease/etiology , Hepatic Veno-Occlusive Disease/metabolism , Hepatic Veno-Occlusive Disease/mortality , Hepatic Veno-Occlusive Disease/pathology , Hepatic Veno-Occlusive Disease/therapy , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Male , Risk Factors , Sirolimus/adverse effects , Sirolimus/therapeutic use , Time FactorsABSTRACT
GVHD remains a major source of morbidity and mortality after allogeneic BMT. GVHD is mediated by alloreactive T cells derived from the hematopoietic graft that target host tissues. Pre-clinical models have shown that presentation of alloantigens by host DCs results in the activation of donor-derived T cells that mediate GVHD. Strategies that interfere with the Ag-presenting capacity of DCs after allogeneic transplantation may decrease the risk of developing GVHD. Vitamin D is a hormone essential for calcium metabolism that shows immunomodulatory properties. We showed that correction of vitamin D deficiency appeared to mitigate manifestations of GVHD. In pre-clinical studies, we have shown that vitamin D inhibits DC maturation, polarizes T-cell populations toward the expression of Th2 as compared with Th1 cytokines, and blunts allogeneic T-cell proliferation in response to DC stimulation. Exposure to vitamin D resulted in increased expression of IDO, an enzyme responsible for tryptophan metabolism that is upregulated in tolerizing DCs. These data suggest that exposure to vitamin D results in immature DC populations that bias toward tolerizing rather than stimulatory T-cell populations. Vitamin D may therefore have a role in the prevention of GVHD.
