Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning

• Virtually all patients experienced at least 1 significant late effect.
• A unique complication in the very young, dental problems were nearly universal.
• Short stature was commonly observed in patients with metabolic diseases (75%).
• Seventy-two percent of the assessable patients had normal pubertal development.
• Cognitive deficits were more commonly seen with metabolic diseases.

Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.9 years) post-CBT. Patients were conditioned with high-dose chemotherapy using Bu-containing regimens. No patient received total body irradiation. The median age at transplant was 1 year (range, .1 to 2). Diagnoses included inherited metabolic diseases (59.8%), leukemia (17.6%), congenital immune deficiency (20.2%), bone marrow failure/myelodysplastic syndrome (3.9%), and hemoglobinopathy (2%). Among patients surviving 5 years, the overall survival rate at 10 years post-CBT was 93% (95% CI, 84.9 to 96.8). Virtually all patients (98%) experienced at least 1 significant late effect. Most (83.3%) experienced 2 or more late effects, and more than half of the patients (64.7%) experienced 3 or more late effects. The most commonly observed late effects included dental problems (92.2%), short stature (55.9%), cognitive deficits (53.6%), pulmonary dysfunction (18.6%), and abnormal pubertal development (27.9%). This is the first report of late effects of Bu-based conditioning in a cohort of very young patients at the time of transplant. These results will inform clinical care guidelines for long-term follow-up and add to the growing information regarding outcomes of hematopoietic stem cell transplantation.