To assess incidence and risk factors for skin cancer associated with allogeneic hematopoietic stem cell transplantation, we evaluated 1,974 adult allogeneic hematopoietic stem cell transplantation patients from Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute who received transplants between January 1995 and July 2013 for hematologic malignancy and survived at least 100 days. Median age was 51.1 years, and median follow-up time was 3 years. Overall, 119 patients had 221 skin cancers. The incidences of squamous cell carcinomas (incidence rate ratio ¼ 9.8; 95% confidence interval ¼ 7.7e12.3), basal cell carcinomas (incidence rate ratio ¼ 2.5; 95% confidence interval ¼ 1.9e3.2), and melanoma (standardized incidence ratio ¼ 3.3; 95% confidence interval ¼ 1.7e5.9) were elevated in our cohort. In multivariable models, risk factors for squamous cell carcinomas were increased age (P < 0.0001), chronic lymphocytic leukemia (P ¼ 0.02), and chronic graftversus-host disease (P ¼ 0.0002). Risk factors for basal cell carcinomas were chronic lymphocytic leukemia (P ¼ 0.003), reduced-intensity conditioning (P ¼ 0.02), acute graft-versus-host disease (P ¼ 0.03), and chronic graft-versus-host disease (P ¼ 0.003). To our knowledge, previously unreported risk factors in this contemporary cohort include prior CLL for squamous cell carcinoma and basal cell carcinoma and reduced-intensity conditioning for basal cell carcinoma. This study also supports chronic graft-versus-host disease as a risk factor for nonmelanoma skin cancer, particularly squamous cell carcinoma.

The IL-1 superfamily of cytokines and receptors has been studied extensively. However, the specific roles of IL-1 elements in host immunity to cutaneous viral infection remain elusive. In this study, we applied vaccinia virus (VACV) by scarification to IL-1 receptor type 1 knockout mice (IL-1R1−/−) and found that these mice developed markedly larger lesions with higher viral genome copies in skin than wild-type (WT) mice. The phenotype of infected IL-1R1−/− mice was similar to eczema vaccinatum (EV), a severe side effect of VACV vaccination that may develop in humans with atopic dermatitis (AD). Interestingly, the impaired cutaneous response of IL-1R1−/− mice did not reflect a systemic immune deficiency, since immunized IL-1R1−/− mice survived subsequent lethal VACV intranasal challenge, or defects of T cell activation or T cell homing to the site of inoculation. Histologic evaluation revealed that VACV infection and replication after scarification were limited to the epidermal layer of WT mice, whereas lack of IL-1R1 permitted extension of VACV infection into dermal layers of the skin. We explored the etiology of this discrepancy and determined that IL-1R1−/− mice contained significantly more macrophages and monocyte-derived dendritic cells (mo-DC) in the dermis after VACV scarification. These cells were vulnerable to VACV infection and may augment the transmission of virus to adjacent skin, thus leading to larger skin lesions and satellite lesions in IL-1R1−/− mice. These results suggest new therapeutic strategies for treatment of EV and inform assessment of risks in patients receiving IL-1 blocking antibodies for treatment of chronic inflammatory disorders.

The authors plan to increase awareness of the EP 2.0 template by educating promotions committees and faculty at UCSF and partnering with other institutions to disseminate it for use. They also plan to study the impact of the template on supporting educators by making their important scholarly contributions available for peer review, providing guidance for professional development, and decreasing disparities in promotions.