Non‐conditioned cord blood transplantation for infection control in athymic CHARGE syndrome

Abstract Objective CHARGE syndrome is a congenital malformation syndrome caused by heterozygous mutations in the CHD7 gene. Severe combined immunodeficiency (SCID) arises from congenital athymia called CHARGE/complete DiGeorge syndrome. While cultured thymus tissue implantation (CTTI) provides an immunological cure, hematopoietic cell transplantation (HCT) is an alternative option for immuno‐reconstitution of affected infants. We aimed to clarify the clinical outcomes of patients with athymic CHARGE syndrome after HCT. Methods We studied the immunological reconstitution and outcomes of four patients who received non‐conditioned unrelated donor cord blood transplantation (CBT) at Kyushu University Hospital from 2007 to 2022. The posttransplant outcomes were compared with the outcomes of eight reported patients. Results Four index cases received CBT 70–144 days after birth and had no higher than grade II acute graft‐versus‐host disease. One infant was the first newborn‐screened athymic case in Japan. They achieved more than 500/μL naïve T cells with balanced repertoire 1 month post transplant, and survived more than 12 months with home care. Twelve patients including the index cases received HCT at a median 106 days after birth (range: 70–195 days). One‐year overall survival rate was significantly higher in patients who underwent non‐conditioned HCT than in those who received conditioned HCT (100% vs. 37.5%, p = .02). Nine patients died, and the major cause of death was cardiopulmonary failure. Conclusions Athymic infants achieved a prompt reconstitution of non‐skewing naïve T cells after non‐conditioned CBT that led to home care in infancy without significant infections. Non‐conditioned CBT is a useful bridging therapy for newborn‐screened cases toward an immunological cure by CTTI.