Citations

BACKGROUNDUmbilical cord blood (UCB) units collected from African Americans (AAs) have lower total nucleated cell (TNC) and CD34+ cell counts and are more likely to disqualify for banking compared to other ethnic groups. Furthermore, AAs have higher prevalence of 25‐hydroxyvitamin D (25(OH)D) deficiency. Given the importance of 25(OH)D in hematopoiesis, we examined the racial differences in UCB unit 25(OH)D content and its correlation with UCB cellular characteristics.STUDY DESIGN AND METHODSA total of 119 UCB units that did not meet the TNC count banking criteria were analyzed. Fifty‐one UCB units were collected from AA mothers and 68 from Caucasian mothers. We analyzed UCB volume, hematocrit (Hct), TNCs, mononuclear cells (MNCs), CD34+ cells, plasma 25(OH)D concentration, and progenitor clonogenic capacity measured by colony‐forming cell (CFC) assay.RESULTSCompared to Caucasians, AAs had significantly lower UCB 25(OH)D levels (p < 0.0001), TNCs (p = 0.002), MNCs (p = 0.026), and CD34+ cells (p = 0.026). Severe deficiency (25(OH)D < 10 ng/mL) was only detected in AAs. No difference in median CFC count/10,000 MNCs was detected between AAs and Caucasians. Independent of race, a significant association was detected between 25(OH)D level and TNCs (r = 0.193 p = 0.035) and Hct (r = 0.196 p = 0.033).CONCLUSIONThese results indicate the importance of 25(OH)D level as a racially independent predictor of UCB cellular characteristics and support further investigation of bioactive vitamin D and other predictors of hematopoiesis on cord blood quality.

SummaryData from the National LymphoCare Study (a prospective, multicentre registry that enrolled follicular lymphoma (FL) patients from 2004 to 2007) were used to determine disease characteristics, treatment patterns, outcomes and prognosis for elderly FL (eFL) patients. Of 2650 FL patients, 209 (8%) were aged >80 years; these eFL patients more commonly had grade 3 disease, less frequently received chemoimmunotherapy and anthracyclines, and had lower response rates when compared to younger patients. With a median follow‐up of 6.9 years, 5‐year overall survival (OS) for eFL patients was 59%; 38% of deaths were lymphoma‐related. No treatment produced superior OS among eFL patients. In multivariate Cox models, anaemia, B‐symptoms and male sex predicted worse OS (P < 0·01); a prognostic index of these factors (0, 1 or ≥2 present) predicted OS [hazard ratio (95% CI): ≥2 vs. 0, 4·72 (2·38–9·33); 1 vs. 0, 2·63 (1·39–4·98)], with a higher concordance index (0·63) versus the Follicular Lymphoma International Prognostic Index (0·55). The index was validated in an independent cohort. In the largest prospective US‐based eFL cohort, no optimal therapy was identified and nearly 40% of deaths were lymphoma‐related, representing baseline outcomes in the modern era.

ObjectiveTo develop general and site‐specific treatment effect and outcome measures to standardize the reporting of head and neck lymphatic malformation (HNLM) treatments.Study DesignConsensus statement/expert opinion.SettingMultiple tertiary academic institutions.Subjects and MethodsThe modified Delphi method is an iterative process of collecting expert opinions, refining opinions through discussion and feedback, statistically aggregating opinions, and using these aggregates to generate consensus opinion in the absence of other data. The modified Delphi method was used by a multi‐institutional group of otolaryngology and interventional radiology experts in the field of vascular anomalies to formulate a list of recommended reporting outcomes for the study and treatment of head and neck lymphatic malformations.ResultsThrough 3 rounds of iteration, 10 expert panelists refined 98 proposed outcome measures and 9 outcome categories to a final consensus set of 50 recommended outcome measures in 3 global categories (general, demographics, and treatment complications) and 5 site‐specific categories (orbit, oral cavity, pharynx, larynx, and neck).ConclusionsWe propose the first consensus set of standardized reporting measures for clinical and treatment outcomes in studies of HNLMs. Consistent outcome measures across future studies will facilitate comparison of treatment options and allow systematic review. We hope that these guidelines facilitate the design and reporting of subsequent HNLM studies.

Abstract Purpose: Oncolytic herpes simplex viruses (oHSV) represent a promising therapy for glioblastoma (GBM), but their clinical success has been limited. Early innate immune responses to viral infection reduce oHSV replication, tumor destruction, and efficacy. Here, we characterized the antiviral effects of macrophages and microglia on viral therapy for GBM. Experimental Design: Quantitative flow cytometry of mice with intracranial gliomas (±oHSV) was used to examine macrophage/microglia infiltration and activation. In vitro coculture assays of infected glioma cells with microglia/macrophages were used to test their impact on oHSV replication. Macrophages from TNFα-knockout mice and blocking antibodies were used to evaluate the biologic effects of TNFα on virus replication. TNFα blocking antibodies were used to evaluate the impact of TNFα on oHSV therapy in vivo. Results: Flow-cytometry analysis revealed a 7.9-fold increase in macrophage infiltration after virus treatment. Tumor-infiltrating macrophages/microglia were polarized toward a M1, proinflammatory phenotype, and they expressed high levels of CD86, MHCII, and Ly6C. Macrophages/microglia produced significant amounts of TNFα in response to infected glioma cells in vitro and in vivo. Using TNFα-blocking antibodies and macrophages derived from TNFα-knockout mice, we discovered TNFα-induced apoptosis in infected tumor cells and inhibited virus replication. Finally, we demonstrated the transient blockade of TNFα from the tumor microenvironment with TNFα-blocking antibodies significantly enhanced virus replication and survival in GBM intracranial tumors. Conclusions: The results of these studies suggest that FDA approved TNFα inhibitors may significantly improve the efficacy of oncolytic virus therapy. Clin Cancer Res; 21(14); 3274–85. ©2015 AACR.

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