Divinity School

Clinical research in children is increasing. Concerns have been raised about both the inclusion and the exclusion of children in such research. Corresponding to these concerns, issues in informed consent for pediatric trials have become more pressing. This review discusses informed consent in pediatric trials and characterizes the latest literature.

HSCT vs. 60% of non-HSCT admissions survived 6 months (p < .0001). Among admissions with an abnormal chest radiograph and a PaO 2 /FIO 2 ratio <200, pediatric intensive care unit survival increased for each successive time period, with 45% of HSCT and 83% of non-HSCT admissions surviving during 2002-2004. In multivariate analysis of all study patients, Pediatric Risk of Mortality scores on the day of intubation, allogeneic HSCT, cardiovascular failure, hepatic failure, neurologic failure, a previous course of mechanical ventilation within 6 months, and the time period intubated were associated with mortality. With the exception of time period, these same variables were associated with mortality in multivariate analysis of only HSCT patients.

Neuroblastoma, a solid tumor arising from developing cells of the sympathetic nervous system, is the most common extracranial tumor in children. The prognosis for high-risk neuroblastoma remains poor with conventional treatment, and new approaches are therefore being explored to treat this disease. One such alternative therapy that holds promise is immune therapy. We review here the recent advances in 4 types of immune therapy-cytokine, vaccine, antibody and cellular therapy-to treat neuroblastoma. We present preclinical research and clinical trials on several promising candidates such as IL-12, dendritic cell vaccines, anti-GD2 antibodies and allogeneic hematopoietic stem cell transplant. An optimal treatment plan for neuroblastoma will most likely involve multimodal approaches and combinations of immune therapies.

Objective: To identify perceived barriers to capacity building for local research ethics oversight in El Salvador, and to set an agenda for international collaborative capacity building. Methods: Focus groups were formed in El Salvador which included 17 local clinical investigators and members of newly formed research ethics committees. Information about the proposed research was presented to participants during an international bioethics colloquium sponsored and organized by the St. Jude Children's Research Hospital in collaboration with the National Ethics Committee of El Salvador and the University of El Salvador. Interviews with the focus group participants were qualitatively analyzed. Results: Participants expressed the need to tailor the informed consent process and documentation to the local culture; for example, allowing family members to participate in decision-making, and employing shorter consent forms. Participants indicated that economic barriers often impede efforts in local capacity building. Participants valued international collaboration for mutual capacity building in research ethics oversight. Conclusions: Research ethics committees in El Salvador possess a basic knowledge of locally relevant ethical principles, though they need more training to optimize the application of bioethical principles and models to their particular contexts. Challenges increase the value of collaborative exchanges with ethics committee members in the United States. Further research on facilitating communication between host country and sponsor country ethics committees can maximize local research ethics expertise, and thus raise the standard of protecting human participants involved in international research.

All allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (HSCT) recipients at St. Jude Children’s Research Hospital undergo pre-HSCT computed tomography (CT) of the sinuses, chest, and abdomen because they are at significant risk for opportunistic infections. We studied whether this extensive routine imaging is warranted to detect infection despite the risk of additional radiation exposure. We reviewed the medical records of all children receiving allo- and auto-HSCT at St. Jude in 2004 and 2005. Of the 184 eligible patients who received 187 transplants, 131 received allografts and 56 autografts. Solid tumors and lymphomas were removed from the final analysis of the chest and abdomen CT as this imaging is typically warranted as part of disease restaging; thus 111 allogeneic participants were included in this analysis. Both auto and allo-recipients were evaluated by sinus CT and included in this final analysis. Most allo- and auto-HSCT recipients (≥ 80%) did not have sinus, pulmonary, cardiac, or gastrointestinal symptoms; >85% of the evaluable allo-recipients had no prior fungal infection. Eighty-eight allo- and 31 auto-HSCT recipients had abnormal sinus CT findings, all unrelated to the underlying disease. Sixty-two (55.9%) of the allo-recipients had normal chest CT and 85 (76.6%) had normal abdominal CT. Of the 18 allo-recipients who began new therapy based on these findings, only 2 (11.1%) were related to chest CT findings and the other 16 were related to sinus findings. Our findings suggest that pre-HSCT routine CT imaging of the abdomen may not be warranted in a subset of allogeneic recipients who are asymptomatic and without previous infectious findings. Thus, these patients may be spared unnecessary radiation exposure. Recipients undergoing auto-HSCT or allo-HSCT for lymphomas or solid tumors will routinely undergo chest and abdominal CT imaging as part of their disease evaluation. The decision to perform chest CT should be made judiciously based on a careful history and physical examination. Sinus imaging, which was frequently abnormal, may be justified in all patients to plan post-HSCT care.