Children undergoing hematopoietic cell transplantation (HCT) for nonmalignant disorders are increasingly surviving long-term, shifting the focus from procedural success to durable immune recovery, infection prevention, revaccination, organ health, development, and quality of life. General pediatricians play a central role in shared care after HCT, as children transition from transplant-centered monitoring back to community-based care. Post-HCT immune recovery is heterogeneous and depends on diagnosis, donor source, graft source, conditioning, serotherapy exposure, graft-versus-host disease (GVHD), immunosuppression, and prior infections. Infection risk persists beyond neutro-phil recovery and may be prolonged in children with delayed T-cell or B-cell recovery, chronic GVHD, or ongoing immunosuppression. Revaccination is essential, as pretrans-plant immunity is often lost. This review provides a practical framework for pediatricians caring for children after nonmalignant HCT, with emphasis on infection prevention, immunization, survivorship monitoring, and the emerging role of data-driven tools to support individualized follow-up.
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.
Hemoglobinopathies are inherited disorders of hemoglobin structure or production. Sickle cell disease (SCD) results from a beta-globin mutation causing hemoglobin polymerization, red blood cell sickling, vaso-occlusion, and hemolytic anemia. Thalassemia results from reduced or absent alpha- or beta-globin synthesis, ranging from asymptomatic carrier states to transfusion-dependent anemia. This article summarizes the pathophysiology, diagnosis, management, and curative options for SCD and transfusion-dependent thalassemia, emphasizing allogeneic hematopoietic stem cell transplantation and approved gene therapies. We discuss indications, counseling, barriers to access, toxicity, donor availability, fertility counseling, and comparative features of cellular therapies. Advances in transplantation, gene addition, and gene editing may expand access to curative-intent therapy and improve outcomes for selected patients.
Primary immunodeficiencies, now more broadly termed as "inborn errors of immunity (IEI)," are rare genetic disorders associated with recurrent infections, immune dysregulation, autoimmunity, lymphoproliferation, and malignancy risk. Early recognition and diagnosis are essential to reduce infection-related morbidity, prevent organ damage, and identify children who may benefit from curative therapy. A comprehensive history, physical examination, targeted immune evaluation, and genetic testing can support diagnosis, while early supportive measures may reduce infection risk before definitive therapy. Treatment may include antimicrobial prophylaxis, immunoglobulin replacement, enzyme replacement, immune-modifying agents, gene-based therapies, and allogeneic hematopoietic cell transplantation (HCT), which can be curative for select IEI. However, HCT requires careful pretransplant evaluation, as outcomes are influenced by disease biology, infection burden, organ function, donor availability, graft-versus-host disease risk, and conditioning toxicity. This review focuses on recognition of IEI, initial evaluation, supportive care, and pre-HCT management for pediatricians.
