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TPS235 Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker for non-invasive longitudinal monitoring of tumor progression in cancer management. Through the recent advances in next generation sequencing (NGS) technologies and personalized assays, ctDNA has been heralded as a promising tool to detect residual disease, relapse, and monitor treatment response in hematologic malignancies and solid tumors. Our study aims to determine whether treatment related ctDNA dynamics can be used as a reliable indicator to predict pathologic complete response (pCR) in patients with rectal cancer receiving neoadjuvant treatment. Methods: This is a prospective observational cohort study. The primary aim is to estimate the sensitivity and specificity of ctDNA clearance in predicting pCR in patients undergoing neoadjuvant therapy. The secondary aim is to evaluate the feasibility of using ctDNA as a surveillance method to detect progression of rectal cancer during neoadjuvant therapy and relapse in the subsequent follow up period. ctDNA levels are collected from newly diagnosed rectal cancer patients at 7 discrete time points: at diagnosis or screening, during neoadjuvant therapy, after completion of neoadjuvant therapy and 1 month, 2 months, 4 months, 6 months after surgery. This will be followed by every 3 months ctDNA testing for surveillance for up to 2 years. We expect to enroll approximately 30 patients at our institution. The subjects will be sorted into two groups: responders and non-responders based on whether they achieve pCR. ctDNA level between two groups will subsequently be compared. The use of ctDNA to predict pCR in rectal cancer patients may allow for many of these patients to safely avoid surgery if undetectable ctDNA at the end of neoadjuvant therapy strongly correlates with pCR. We are actively enrolling patients into this prospective observational study and expect to report the data in the near future. The data we obtain will be combined with those from several institutions around the US doing similar studies with the same test. Data analysis will subsequently be conducted. [Table: see text]

Children, adolescents, and young adults with chronic refractory autoimmune cytopenias represent a rare but challenging group of patients, who are managed frequently by pediatric hematologists. Novel diagnostic tests and genomic discoveries are refining historical diagnoses of Evans syndrome and common variable immunodeficiency, while also elucidating the cellular and molecular basis for these disorders. Genetic characterization of chronic and refractory autoimmune cytopenias has led to targeted therapies with improved clinical outcomes and fewer off-target toxicities. In this review, we focus on the appropriate diagnostic workup, expanded genetic testing, and novel treatment opportunities that are available for these challenging patients.

Background The acute chest syndrome is the leading cause of death among patients with sickle cell disease. Since its cause is largely unknown, therapy is supportive. Pilot studies with improved diagnostic techniques suggest that infection and fat embolism are underdiagnosed in patients with the syndrome. Methods In a 30-center study, we analyzed 671 episodes of the acute chest syndrome in 538 patients with sickle cell disease to determine the cause, outcome, and response to therapy. We evaluated a treatment protocol that included matched transfusions, bronchodilators, and bronchoscopy. Samples of blood and respiratory tract secretions were sent to central laboratories for antibody testing, culture, DNA testing, and histopathological analyses. Results Nearly half the patients were initially admitted for another reason, mainly pain. When the acute chest syndrome was diagnosed, patients had hypoxia, decreasing hemoglobin values, and progressive multilobar pneumonia. The mean length of hospitalization was 10.5 days. Thirteen percent of patients required mechanical ventilation, and 3 percent died. Patients who were 20 or more years of age had a more severe course than those who were younger. Neurologic events occurred in 11 percent of patients, among whom 46 percent had respiratory failure. Treatment with phenotypically matched transfusions improved oxygenation, with a 1 percent rate of alloimmunization. One fifth of the patients who were treated with bronchodilators had clinical improvement. Eighty-one percent of patients who required mechanical ventilation recovered. A specific cause of the acute chest syndrome was identified in 38 percent of all episodes and 70 percent of episodes with complete data. Among the specific causes were pulmonary fat embolism and 27 different infectious pathogens. Eighteen patients died, and the most common causes of death were pulmonary emboli and infectious bronchopneumonia. Infection was a contributing factor in 56 percent of the deaths. Conclusions Among patients with sickle cell disease, the acute chest syndrome is commonly precipitated by fat embolism and infection, especially community-acquired pneumonia. Among older patients and those with neurologic symptoms, the syndrome often progresses to respiratory failure. Treatment with transfusions and bronchodilators improves oxygenation, and with aggressive treatment, most patients who have respiratory failure recover.

Hepatocellular carcinoma (HCC) is a challenging malignancy as a result of the advanced course at presentation. Recent interventional advances have improved treatment of lesions unamenable to resection using drug-eluting microbeads delivered into the hepatic circulation. We hypothesize that the use of hepatic arterial therapy (HAT) will safely identify appropriate patients who can proceed to ablation and/or transplantation. We evaluated our open-label, multicenter, multinational, single-arm study including 240 patients with intermediate-staged HCC who received drug-eluting beads and were not initial candidates for transplantation or resection. We reviewed the resulting clinical data to determine factors leading to possible ablation or transplant. Of 240 patients undergoing HAT, 14 (5.8%) received ablation or transplant. We compared those receiving ablation or transplant with those receiving only HAT. Groups were similar regarding sex, age, median number of tumors (one; range, 1 to 25), Child's score, tobacco and alcohol abuse, and treatment type. Patients who were downstaged were more likely to have: hepatitis-related tumors (76 to 66%, P = 0.02), distinct lesions on imaging (92 to 76%, P = 0.004), and less than 25 per cent parenchymal involvement (84 to 59%, P = 0.0001). These patients typically had one tumor frequently in the left lobe (58.8 vs 30.9%, P = 0.0001), accessible through segmental arteries (47 vs 17%, P = 0.001), with increased segmental branch occlusion (57 vs 39%, P = 0.02). HAT should be considered a potential bridging therapy to eventual ablation or transplant in the multimodal treatment of HCC.