Outcome and Risk Factors of Autoimmune Cytopenia after Hematopoietic Cell Transplantation for Children with Primary Immunodeficiency (original) (raw)

Relative to low cell dose therapies, transplant of MGTA-456, a high cell dose therapy with two normal IDUA gene copies, led to robust, long-term immune recovery (n=88 animals), 60-fold greater microglial engraftment as early as 2 weeks post-HSCT (Figure D, p<0.001), and >600-fold higher IDUA enzyme levels (Figure E, p<0.001). MGTA-456 enabled use of low-dose busulfan, with 21-fold greater microglial engraftment than that achieved by standard approaches using high-dose busulfan (p<0.01, n=8). Mechanistically, brain microglia are derived from CD34+CD90+ cells, which are present at high numbers in MGTA-456. Conclusions: We show that high dose HSCT leads to improved disease correction, including normalization of behavioral outcomes, via robust engraftment. High dose cell therapies, like MGTA-456, may rapidly and durably resolve peripheral and neurologic disease in patients with IMDs and other neurodegenerative diseases caused by defective microglia.