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Key Points Over the last decade, allogeneic HCT has been increasingly administered in the United States to adults aged 70 and older with hematologic malignancies. Allogeneic transplant outcomes were reasonable; high comorbidity and ablative conditioning regimens were associated with inferior outcomes.

Investigating the most likely causal variants identified by fine‐mapping analyses may improve the power to detect gene–environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine‐scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER negative (ER–) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results. Four potential gene–environment interactions were identified as noteworthy (BFDP < 0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR‐rs7558475 and current smoking (ORint = 0.77, 95% CI: 0.67–0.88, pint = 1.8 × 10−4). The interaction with the strongest statistical evidence was found between 5q14‐rs7707921 and alcohol consumption (ORint =1.36, 95% CI: 1.16–1.59, pint = 1.9 × 10−5) in relation to ER– disease risk. The remaining two gene–environment interactions were also identified in relation to ER– breast cancer risk and were found between 3p21‐rs6796502 and age at menarche (ORint = 1.26, 95% CI: 1.12–1.43, pint =1.8 × 10−4) and between 8q23‐rs13267382 and age at first full‐term pregnancy (ORint = 0.89, 95% CI: 0.83–0.95, pint = 5.2 × 10−4). While these results do not suggest any strong gene–environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed.

Objective: To summarize the epidemiology and outcomes of children with multiple organ dysfunction syndrome as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development multiple organ dysfunction syndrome workshop (March 26–27, 2015). Data Sources: Literature review, research data, and expert opinion. Study Selection: Not applicable. Data Extraction: Moderated by an experienced expert from the field, issues relevant to the epidemiology and outcomes of children with multiple organ dysfunction syndrome were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities. Data Synthesis: Summary of presentations and discussion supported and supplemented by the relevant literature. Conclusions: A full understanding the epidemiology and outcome of multiple organ dysfunction syndrome in children is limited by inconsistent definitions and populations studied. Nonetheless, pediatric multiple organ dysfunction syndrome is common among PICU patients, occurring in up to 57% depending on the population studied; sepsis remains its leading cause. Pediatric multiple organ dysfunction syndrome leads to considerable short-term morbidity and mortality. Long-term outcomes of multiple organ dysfunction syndrome in children have not been well studied; however, studies of adults and children with other critical illnesses suggest that the risk of long-term adverse sequelae is high. Characterization of the long-term outcomes of pediatric multiple organ dysfunction syndrome is crucial to identify opportunities for improved treatment and recovery strategies that will improve the quality of life of critically ill children and their families. The workshop identified important knowledge gaps and research priorities intended to promote the development of standard definitions and the identification of modifiable factors related to its occurrence and outcome.

LBA7006 Background: PAC is a potent JAK2 inhibitor without significant JAK1 inhibition with minimal myelosuppression in early-phase studies in MF. Methods: The efficacy and safety of daily oral PAC was compared to BAT (2:1 randomization stratified for risk and platelet count). The 10 endpoint was the proportion of ITT patients (pts) achieving ≥ 35% spleen volume reduction (SVR) at week (wk) 24 by centrally reviewed MRI or CT. Secondary endpoints included the proportion achieving ≥ 50% reduction in total symptom score (TSS) at wk 24 using the MPN Symptom Assessment Form. Results: Patients:327 were enrolled (PAC:220, BAT:107), 62% with 10 MF. Median time from diagnosis was 1.12 years (PAC 0.99, BAT 1.60): 32% and 15% had a platelet counts < 100,000/µL or <50,000/ µL; 75% were JAK2V617F positive. Efficacy: The median duration of treatment was 16.2 months PAC and 5.9 months BAT. Sixty-two percent of BAT patients received active disease directed therapy. The SVR rates at week 24 were 19.1% for PAC vs. 4.7% for BAT (p=0.0003) in ITT and 25% vs. 5.9% (p=0.0001) in the evaluable population. 79% of BAT patients crossed over to PAC; 21% had achieved a >35% reduction in spleen volume at data cutoff. TSS composite V1 + V2 response rates were 24.5%for PAC vs. 6.5% for BAT (p<0.0001) by ITT, and were 40.9% vs. 9.9% in evaluable pts (p<0.0001). Efficacy with baseline cytopenias: In pts with <100,000 and <50,000 platelets/μ/L, the SVR rates were 16.7% for PAC vs. 0% for BAT (p=0.009), and 22.9% vs. 0% (p=0.045) by ITT and 23.5% vs. 0% (p=0.007) and 33.3% vs. 0% (p=0.037) in evaluable pts. In RBC transfusion dependent pts, 25.7% of PAC pts became RBC independent vs. 0% of BAT pts (p=0.043). Safety: The most common adverse events (AE) for PAC were diarrhea, nausea, and vomiting; (grade 3 were <5%, <1%, <1% respectively). Hematologic AEs were similar between PAC and BAT. Conclusions: This study demonstrated PAC was well tolerated and induced significant and sustained SVR and symptom control even in patients with severe thrombocytopenia. PAC therapy resulted in RBC transfusion independence in a significant proportion of pts. Clinical trial information: NCT01773187.

PURPOSE: The current American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) fails to stratify patients adequately with respect to prognosis. PATIENTS AND METHODS: The ability of the currently proposed tumor (T) categories to effectively stratify the survival of 557 patients who underwent complete resection for HCC at four centers was examined. Independent predictors of survival were combined into a new staging system. RESULTS: Using the current AJCC T classification, patients with T1 and T2 tumors had similar 5-year survivals (P = .6). In addition, the survival of patients with multiple bilobar tumors (T4) matched that of T3 patients (P = .5). Independent predictors of death were major vascular invasion (P < .001), microvascular invasion (P = .001), severe fibrosis/cirrhosis of the host liver (P = .001), multiple tumors (P = .007), and tumor size greater than 5 cm (P = .01). Based on our results, a simplified stratification is proposed: (a) patients with a single tumor and no microvascular invasion, (b) patients with a single tumor and microvascular invasion or multiple tumors, none more than 5 cm, and (c) patients with either multiple tumors, any more than 5 cm, or tumor with major vascular invasion (P < .001). Severe fibrosis/cirrhosis had a negative impact on survival within all categories. The survival of patients with lymph node involvement matched that of patients with major vascular invasion (P = .3). CONCLUSION: The current AJCC staging system for HCC is unnecessarily complex. We propose a simplified model of stratification that is based on vascular invasion, tumor number, and tumor size and incorporates the effect of fibrosis on survival.