Pediatric Bone Marrow Failure Network (pBMFN)

About This Grant

Project Summary / Abstract – OVERALL Bone marrow failure (BMF), also called aplastic anemia, is a rare disorder in which a hypocellular marrow produces insufficient blood cells. Most cases result from immune-mediated destruction of hematopoietic progenitor cells or genetic disorders of hematopoiesis, but a subset of patients have no identifiable etiology. There is an unmet need to understand pediatric BMF as a biologically and clinically distinct entity from adult disease. The developing pediatric immune system and rarity of baseline clonal hematopoiesis contrasts with the age-associated clonal hematopoiesis and more inflammatory marrow environment of the aging adult immune system. Consequently, disease biology, treatment outcomes and long-term complications differ substantially between children and adults, yet data to guide the diagnosis and management of pediatric BMF remain sparse. Current clinical and laboratory parameters inadequately predict clinical outcomes and risk of infections, relapse, and treatment-related toxicities. To address these barriers, we will establish the Pediatric BMF Network (pBMFN), a national partnership that unites the established North American Pediatric Aplastic Anemia Consortium (NAPAAC) with the Rare Disease Clinical Research Network (RDCRN). The pBMFN will focus on three rare BMF diseases: acquired severe aplastic anemia (Project 1), idiopathic BMF (Project 2), and paroxysmal nocturnal hemoglobinuria (Project 3). These conditions share high morbidity, poorly defined natural history in children, limited data on treatment selection and timing of hematopoietic stem cell transplantation, and a scarcity of disease experts. The pBMFN integrates multidisciplinary expertise in hematology, hematopoietic stem cell transplantation, immunology, hematopathology, genetics, biostatistics, and data science in a unified infrastructure. Each project will define the natural history and prospectively analyze immunologic signatures with multi-modal data linked to a uniform set of clinical phenotype data to delineate disease mechanisms and risk stratification for improving clinical care. Partnership with the Patient Advocacy Group (PAG) will ensure that research priorities and study designs reflect patient and family perspectives. Three cross-cutting cores will strengthen this effort. The Career Enhancement Core will develop educational activities and resources for trainees as well as for the medical and lay communities. The Pilot/Feasibility Core will identify and support high- impact projects from early career investigators to catalyze innovation in pBMF. The Administrative Core will oversee network operations and coordination with the RDCRN and DMCC, NAPAAC, PAGs, and External Advisory Board. Through harmonized diagnostics, standardized data capture, and linked biospecimen collection, the pBMFN will generate enduring clinical and biologic resources to define disease mechanisms and categories, risk stratification, and foster clinical trial readiness. These efforts will transform the care of children with rare BMF disorders by advancing precision diagnostics, improved clinical outcomes, and the infrastructure needed for curative treatments.