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Abstract: A graft-versus-tumor effect through nonmyeloablative allogeneic stem cell transplantation (N-SCT) in metastatic renal cell carcinoma (RCC) has been reported. An Intergroup phase II trial was undertaken to define further the feasibility, toxicity and efficacy of this approach in a multi-institutional setting, Patients with cytokine-refractory, metastatic RCC were treated with N-SCT. The conditioning regimen was fludarabine 30 mg·m−2 ·d−1 on day (d) −7 through d −3 and cyclophosphamide 60 mg·kg−1 ·d−1 on d −4 and d −3. Patients received 2-8 × 106 CD34+ cells/kg of granulocyte colony-stimulating factor mobilized stem cells from a 6/6 HLA-matched sibling donor. Immunosuppression after transplantation included tacrolimus and methotrexate. Twenty-two patients were enrolled at 14 institutions. Greater than 90% donor T-cell chimerism was observed in 17 of 19 evaluable patients (89%) by d +120. No objective response was observed. Acute graft-versus-host disease (GVHD) was observed in 11 patients (50%). Chronic GVHD was reported in 5 patients (23%). There was 1 patient death from liver failure secondary to chronic GVHD. Regimen-related mortality was 2 of 22 (9%; liver failure, sepsis). Median survival time was 5.5 months (95% confidence interval, 3.9-12.0 months) and the median time to progression was 3.0 months (95% confidence interval, 2.3-4.2 months). N-SCT for metastatic RCC is feasible in a multi-institutional setting. Adequate donor T-cell engraftment was achieved in most patients before disease progression. A graft-versus-tumor effect was not observed in this study despite acute and chronic GVHD, thus highlighting the need for further understanding of this approach. Allogeneic SCT remains investigational in RCC. [Copyright &y& Elsevier]

Abstract: Detailed Spanish records of mercury use and silver production during the colonial period in Potosí, Bolivia were evaluated to estimate atmospheric emissions of mercury from silver smelting. Mercury was used in the silver production process in Potosí and nearly 32,000 metric tons of mercury were released to the environment. AERMOD was used in combination with the estimated emissions to approximate historical air concentrations of mercury from colonial mining operations during 1715, a year of relatively low silver production. Source characteristics were selected from archival documents, colonial maps and images of silver smelters in Potosí and a base case of input parameters was selected. Input parameters were varied to understand the sensitivity of the model to each parameter. Modeled maximum 1-h concentrations were most sensitive to stack height and diameter, whereas an index of community exposure was relatively insensitive to uncertainty in input parameters. Modeled 1-h and long-term concentrations were compared to inhalation reference values for elemental mercury vapor. Estimated 1-h maximum concentrations within 500 m of the silver smelters consistently exceeded present-day occupational inhalation reference values. Additionally, the entire community was estimated to have been exposed to levels of mercury vapor that exceed present-day acute inhalation reference values for the general public. Estimated long-term maximum concentrations of mercury were predicted to substantially exceed the EPA Reference Concentration for areas within 600 m of the silver smelters. A concentration gradient predicted by AERMOD was used to select soil sampling locations along transects in Potosí. Total mercury in soils ranged from 0.105 to 155 mg kg−1, among the highest levels reported for surface soils in the scientific literature. The correlation between estimated air concentrations and measured soil concentrations will guide future research to determine the extent to which the current community of Potosí and vicinity is at risk of adverse health effects from historical mercury contamination. [Copyright &y& Elsevier]