Clinical trials commonly use adjudication committees to refine endpoints, but observational research or genome-wide association studies rarely do. Our goals were to establish definitions of cause-specific death after unrelated donor allogeneic hematopoietic cell transplantation (URD-HCT), estimate discordance between reported and adjudicated cause-specific death, and identify factors contributing to inconsistency in cause-specific deathdetermination. A consensus panel adjudicated cause-specific deathin 1,484 patients who died within 1 year after HCT, derived from 3,532 acute leukemia or myelodysplasia patients after URD-HCT 2000-2011 reported by 151 U.S. transplant centers to CIBMTR. Deaths were classified as disease-related (DRM) or transplant-related (TRM). The panel agreed with >99% of deaths reported by centers as DRM and 80% reported as TRM. Year of transplant (cohort effect) and disease status significantly influenced agreement between panel and centers. Sensitivity analysis of deaths <100 days post-transplant yielded lowest agreement between the panel and centers for myelodysplastic syndrome patients. Standard pre-defined criteria for adjudicating cause-specific deathled to consistent application to similar clinical scenarios and clearer delineation of cause-specific deathcategories. Other studies of competing events like cancer-specific vs treatment-related mortality would benefit from our results. Our detailed algorithm should result in more consistent reporting of cause-specific deathby centers.

Overall survival following hematopoietic cell transplantation (HCT) has improved over the past two decades through better patient selection and advances in HLA typing, supportive care, and infection prophylaxis. Nonetheless, mortality rates are still unsatisfactory and transplant-related mortality remains a major cause of death after unrelated allogeneic HCT. Since there are no known pre-HCT, non-HLA biologic predictors of survival following transplant, for over a decade, scientists have been investigating the role of non-HLA germline genetic variation in survival and treatment-related mortality after HCT. Variation in single nucleotide polymorphisms (SNPs) has the potential to impact chemotherapy, radiation, and immune responses, leading to different post-HCT survival outcomes. In this paper, we address the current knowledge of the contribution of genetic variation to survival following HCT and discuss study design and methodology for investigating HCT survival on a genomic scale.

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Racial and ethnic disparities have been reported in clinical trial/research participation, utilization of autologous and allogeneic BMT and availability of allogeneic donors. We performed a population-based cohort study to investigate adult hematologic malignancy referrals to a U.S tertiary cancer center, utilization of BMT and participation in clinical trials, survey and biospecimen research, by race. U.S. Census Data and the New York State Public Access Cancer Epidemiology Database identified the racial distribution of the general population and new hematologic malignancy cases in the primary catchment area. From 2005–2011, 1,106 patients aged 18–75 years were referred for BMT consultation; while the rate of BMT among hematologic malignancy referrals did not differ by race, the reasons for not receiving a BMT did. Participation in biospecimen research did not vary by race, however African-Americans and other minorities were significantly less likely to participate in survey research than European-Americans. While rates of hematologic malignancy referrals and use of BMT for minorities appear low (<10%), they closely reflect the race distribution of all hematologic malignancy cases and the Western New York population. African-Americans are equally likely as other races to participate in biospecimen banking, but further study is needed to understand reasons for lower participation in survey research.

BackgroundRegulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.MethodsIn a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.ResultsThe most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with (p = 0.001) and clear cell EOC. Gene associations with histotypes at< 0.05 included:(p = 0.005 and = 0.008, serous and high-grade serous, respectively), (p = 0.035, endometrioid and mucinous), (p = 0.03, mucinous), (p = 0.022, clear cell), (p = 0.021 endometrioid) and (p = 0.017 and = 0.025, endometrioid and mucinous, respectively).ConclusionsCommon inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.