The prevalences of PBC and AIH are of the same order of magnitude and about twice as high as that of PSC. These epidemiologic data can be used to estimate the number of liver transplantations required due to autoimmune liver diseases.

Steroid-refractory chronic graft-vs-host disease (cGvHD) contributes to morbidity after allogeneic hematopoietic stem cell transplantation. Here, we report on 11 patients with severe, refractory cGvHD treated with repeated infusions of allogeneic bone marrow-derived mesenchymal stromal cells (MSC) over a 6-to 12-month period. Six patients responded to MSC treatment following National Institutes of Health response criteria, accompanied by improvement in GvHD-related symptoms and quality of life. This response was durable, with systemic immunosuppressive therapy withdrawn from two responders, and a further two free from steroids and tapering calcineurin inhibitors. All responders displayed a distinct immune phenotype characterized by higher levels of naïve T cells and B cells before treatment compared with the nonresponders, and a significantly higher fraction of CD31+ naïve CD4+ T cells. MSC treatment was associated with significant increases in naïve T cells, B cells, and Tregs 7 days after each infusion. Skin biopsies showed resolution of epidermal pathology. CXCL9 and CXCL10 showed differential responses in responder and nonresponder patients. Our data support the use of MSC infusions as treatment for steroid-refractory cGvHD with durable responses. We propose CXCL9 and CXCL10 as early biomarkers for responsiveness to MSC treatment. Our results highlight the importance of the MSC recipient immune phenotype in promoting treatment response. This trial was registered at www.ClinicalTrials.gov as #NCT01522716.

Bone marrow derived mesenchymal stromal cells (BM-MSCs) have emerged as a possible new therapy for Multiple Sclerosis (MS), however studies regarding efficacy and in vivo immune response have been limited and inconclusive. We conducted a phase I clinical study assessing safety and clinical and peripheral immune responses after MSC therapy in MS. Seven patients with progressive MS were intravenously infused with a single dose of autologous MSC (1–2 × 106 MSCs/kg body weight). The infusions were safe and well tolerated when given during clinical remission. Five out of seven patients completed the follow up of 48 weeks post-infusion. Brain magnetic resonance imaging (MRI) showed the absence of new T2 lesions at 12 weeks in 5/6 patients, while 3/5 had accumulated new T2 lesions at 48 weeks. Patient expanded disability status scales (EDSS) were stable in 6/6 at 12 weeks but declined in 3/5 patients at 48 weeks. Early changes of circulating microRNA levels (2 h) and increased proportion of FOXP3+ Tregs were detected at 7 days post-infusion compared to baseline levels. In conclusion, MSC therapy was safe and well tolerated and is associated with possible transient beneficial clinical and peripheral immunotolerogenic effects.

Objectives: Epidemiologic studies suggest an association between environmental exposure to benzene and hematologic cancers, but the relationship is not firmly established. The aim of this study was to assess the potential association between residence near hazardous waste sites containing benzene and hospitalization discharge rates for persons having hematologic cancers. Materials and Methods: We determined the number of hospital discharges of people with hematologic cancers in New York State except for New York City for the years 1993 to 2008. Descriptive statistics and negative binomial regression models were used to compare the rates of hospitalization of residents in zip codes containing hazardous waste sites containing benzene to the rates of discharges from residents in zip codes without waste sites. Results: When adjusting for potential confounders we found a 15% increase in the rate of hospitalization for chronic lymphatic leukemia (CLL) [rate ratio (RR): 1.15; 95% confidence interval (CI): 1.00-1.33], a 22% increase in the rate of discharges for total leukemia (RR: 1.22; 95% CI: 1.04-1.43) and a 17% increase in the rate of discharges for total lymphoma (RR: 1.17; 95% CI: 1.02-1.35) in the benzene exposed sites. We found greater effects of exposure in African Americans compared to Caucasians, females compared to males and people with higher socioeconomic status (SES) compared to those with lower SES for several of the diseases studied. Conclusions: After controlling for major confounders we found statistically significant increases in discharge rates for several hematologic cancers in persons residing in zip codes containing benzene waste sites. These results provide additional support for a relationship between environmental exposure to benzene and risk of hematologic cancers.