The Northern California Consortium for Sickle Cell Disease is a cohesive network of regional clinics and comprehensive medical centers in Northern California and Nevada that are committed to providing comprehensive care for sickle cell disease. In addition, contributing centers in this Consortium have all the necessary elements that include physicians, nurses, clinical support staff, data coordinators, and clinical research infrastructure necessary to participate successfully in clinical trials for sickle cell disease. Efforts at patient recruitment will be enhanced by a partnership with the Community Advisory Committee, a community-based patient advocate organization in Northern California, by communicating with patients and their families about proposed clinical trials. Two clincal investigations are proposed in this application and involve areas in which the center in Oakland has a strong track record of clinical research. The first is a long-term follow-up evaluation after hematopoietic cell transplantation for sickle cell disease, which will be conducted in collaboration with the Center for International Blood and Marrow Transplantation Research (CIBMTR). This study will include a comparison of outcomes among children enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) and the multicenter pediatric hydroxyurea trial (HUG-KIDS), led by investigators in the Biostatistics team at Rho. The second investigation is a phase III randomized prospective trial of RBC transfusions to prevent acute chest syndrome in sickle cell disease. This investigation will target enrollment of sickle cell disease patients who exhibit high-risk features for acute chest syndrome, as evidenced by elevated levels of secretory phospholipase A2 (sPLA2), an enzyme which cleaves phospholipids generating fatty acids and lysophospholipids. Recently, we demonstrated that sPLA2 is dramatically elevated in many cases of ACS and rising sPLA2 levels predict ACS before it develops. The results of the proposed clinical trials are very likely to have a profound effect on the clinical management of patients with sickle cell disease, and both require a multicenter cooperative clinical trial infrastructure in order to complete these clinical investigations in a timely and rigorous manner.