Outcomes of bone marrow mononuclear cell transplantation combined with interventional education for autism spectrum disorder

Abstract

The aim of this study was to evaluate the safety and efficacy of autologous bone marrow mononuclear cell transplantation combined with educational intervention for children with autism spectrum disorder. An open-label clinical trial was performed from July 2017 to August 2019 at Vinmec International Hospital, Hanoi, Vietnam. Thirty children who fulfilled the autism criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and had Childhood Autism Rating Scale (CARS) scores >37 were selected. Bone marrow was harvested by anterior iliac crest puncture under general anesthesia. The volume collected was as follows: 8 mL/kg for patients under 10 kg (80 mL + [body weight in kg − 10] × 7 mL) for patients above 10 kg. Mononuclear cells were isolated with a Ficoll gradient and then infused intrathecally. The same procedure was repeated 6 months later. After the first transplantation, all patients underwent 8 weeks of educational intervention based on the Early Start Denver Model. There were no severe adverse events associated with transplantation. The severity of autism spectrum disorder (ASD) was significantly reduced, with the median CARS score decreasing from 50 (range 40-55.5) to 46.5 (range 33.5-53.5) (P < .05). Adaptive capacity increased, with the median Vineland Adaptive Behavior Scales score rising from 53.5 to 60.5. Social communication, language, and daily skills improved markedly within 18 months after transplantation. Conversely, repetitive behaviors and hyperactivity decreased remarkably. Autologous bone marrow mononuclear cell transplantation in combination with behavioral intervention was safe and well tolerated in children with ASD (Trial registration: ClinicalTrials.gov identifier: NCT03225651).

Case Report: Autologous Bone Marrow Derived Intrathecal Stem Cell Transplant for Autistic Children - A Report of Four Cases and Literature Review

“…Comparable to our treatment approach applying autologous BM-derived intrathecally applied SCT, two investigations -one applying a single (14) and the other two-intrathecal (15) stem cell instillations also reported encouraging results. Mixed results were reported using intravenous delivery of either, autologous or allogenic, umbilical cord blood-derived SCT.…”

“…Sharma et al (14) in a group of 34 children reported asides minor side effects including nausea, vomiting, and local pain, a percentage of major adverse events in 31% (10/32) comprising hyperactivity and epileptic seizures. Thanh et al (15) reported no major adverse event in similarly sized study on 30 children undergoing repeated interventions. In our pilot study we encountered neither immediate, nor delayed major adverse events.…”

“…This changed paradigm of ASD conception opened the door to introduce biological (autologous or allogenic) stem cell therapies known among others for their immune-modulating properties (12,13). In this context, an increasing number of published investigations reporting on treatment attempts employing either autologous or allogeneic bone marrow (BM) or umbilical derived pluripotent cells (14)(15)(16)(17)(18)(19) have encouraged us to report the results in a pilot group of children. Autologous BM-derived, point-of-care stem cell transplantation (SCT) was used due to the fact that it carries virtually no risk with respect to adverse autoimmune reaction and for its universal availability, as it does not exclude children without stored umbilical cord or access to umbilical cord blood.…”

“…Two studies applying intrathecal instillation of autologous stem cells were reported by Sharma et al (14) from India and Thanh et al (15) from Vietnam in small cohorts. To start a new procedure in a geographical and political part of the world as large as the EU in our opinion warrants the report of small case studies, which undoubtedly should and will be followed by larger studies in due time.…”

Stem Cell Therapies for Cerebral Palsy and Autism Spectrum Disorder—A Systematic Review

“…A clinical study examining the efficacy of autologous bone marrow mononuclear cell transplantation (BMMNC) in thirty children who fulfilled the autism criteria with Childhood Autism Rating Scale (CARS) scores >37 reported a significant reduction in the severity of ASD with the median CARS score decreasing from 50 (range 40–55.5) to 46.5 (range 33.5–53.5) ( p < 0 .05) [ 108 ]. Another study assessing the (BMMNC) transplantation infused via the intrathecal route in 32 children with ASD noticed improvements in speech, language patterns, social relationships, and brain metabolism.…”