Reply

Abstract

ogous cord blood infusions are safe and feasible in young children with autism spectrum disorder: results of a single-center phase I open-label trial. Stem Cells Transl Med 2017;6:1332-9. ReplyTo the Editor:We appreciate the questions raised by Thanh et al about our clinical trial evaluating the safety and efficacy of intravenous umbilical cord blood infusion for the treatment of children with autism spectrum disorder (ASD). We did not target CD34 dosing in this clinical trial because our preclinical studies and early-phase clinical trial data in children with ASD and children with cerebral palsy (CP) did not show any association between improvement and CD34 dosing.Our data showed that the cell responsible for modulation of neuroinflammation, stimulation of oligodendrocyte proliferation, remyelination, and increasing whole brain connectivity is the CD14+ monocyte in cord blood. [1][2][3][4] Cord blood banks do not measure CD14 cell content but do measure total nucleated cells (TNCCs) and CD34. For this reason, selection of cord blood units for the participants with ASD and CP in our clinical trials has been based on TNCC. We are investigating whether infused CD14 cell doses correlate with response but do not have that data at this time.In our first randomized trial using autologous cord blood in young children with CP, we reported an effective dose threshold of 25 million cells/kg. 5 We saw the same trend in our initial phase I trial in children with ASD. 6 Since that time, we have targeted greater TNCC doses in our trials involving children with CP and have observed a dose effect up to 100 million cells/kg (unpublished data). For our trials with children with ASD, we target a minimal dose of 25 million cells/kg. Although CD34 cell dosing is quantitated in all our trials, we have not seen any relationship between CD34 dose and response. The CD34 doses in the trial reported in The Journal are typical of CD34 doses achievable with an unmodified cord blood transplant or cord blood infusion. We are following children in the trial published in The Journal for a period of 12 months postinfusion and will be reporting the 12-month outcome data at a later date.