Pediatric Nonmalignant Hematopoietic Cell Transplantation in the Era of Precision Conditioning and Gene Therapy.
TL;DR
A five-axis framework to guide referral, treatment selection, and survivorship planning is proposed to guide referral, treatment selection, and survivorship planning for pediatric hematopoietic cell transplantation for nonmalignant disorders.
Abstract
The landscape of pediatric hematopoietic cell transplantation for nonmalignant disorders has evolved through disease-adapted conditioning, pharmacokinetic-guided dosing, expanded donor options, and gene therapy (GT). These advances have transformed curative strategies for children with select inborn errors of immunity, hemophagocytic lymphohistiocytosis, hemoglobinopathies, bone marrow failure syndromes, and select metabolic disorders. Early diagnosis, especially newborn screening for severe combined immunodeficiency, enables timely intervention, with contemporary series reporting more than 90% survival in select early-treated infants. Similarly, modern matched related donor transplantation for pediatric severe aplastic anemia approaches 98% 3-year survival. Fludarabine-based platforms combined with busulfan, melphalan, or treosulfan support durable engraftment with reduced toxicity, while matched unrelated, haploidentical, and cord blood donors expand access. GT now offers a parallel curative platform for select sickle cell disease, transfusion-dependent beta-thalassemia, and immunodeficiencies. For pediatricians, early referral before irreversible complications is critical. This review proposes a five-axis framework to guide referral, treatment selection, and survivorship planning.