Table 2.
Published investigations reporting intrathecal or intravenous application of either autologous or allogenic stem cell transplantation for children with autism spectrum disorder (ASD).
| Before 2020 | Sharma et al. (14) | Lv et al. (18) | Dawson et al. (19) | Chez et al. (20) |
|---|---|---|---|---|
| Journal (year) |
Stem Cells 2013 |
J of Transl Med 2013 |
Stem Cells Transl Med 2017 |
Stem Cells Transl Med 2018 |
| Study design |
Open label proof-of-concept, 24 centers |
Controlled, non-randomized, (Phase I/II) |
Single-center phase I, open-label |
Placebo-controlled crossover |
| Patients (n) (gender, age) |
32 (8f/24m; 3-33y) |
37 (1f/36m; 3-12y) |
25 (4f/21m; 2-6y) |
29 (4f/25m; 2-7y) |
| Groups | 32 intervention | 14 UCB 9 UCB+UC 14 controls (therapy) |
25 intervention | 14 intervention 15 placebo |
| SC origin | BM | UCB and UC | UCB | UCB |
| Application route |
Intrathecal | Intravenous (4x) | Intravenous (1x) | Intravenous (1x) |
| Follow-up | 26 months | 4, 8, 16, 24 weeks | 6 and 12 months | 12 and 24 weeks |
| Safety | Minor AE 17.9% vomiting 10.7% nausea 7.1% pain (injection) 7.1% pain (aspiration) 3.6% spinal headache Major AE 6 transient increase In hyperactivity 3 seizures 1 persistent 6 months Increase in hyperactivity |
No major AE 3 minor AE (low grade fever) |
9 related AE 5 allergic reaction 2 agitation 1 aggression 1 other psychiatric disorder No serious AE |
3 “probable” AE 2 renal/urinary disorders 1 constitutional symptom 14 “possible” AE 8 gastrointestinal disorders 4 renal/urinary disorders 2 constitutional symptom No serious AE |
| Efficacy | Sign. improvements of scores (ISAA, CGI, FIM, Wee-FIM) |
Both intervention groups showed sign. improvements (CGI, CARS, ABC) compared to controls |
Sign. improvements of scores (CGI, EOWPVT-4, PDDBI, EGT) | Trend towards improvement of scores (EOWPVT-4, ROWPVT-4, SBFR/SBKN, ABC, CGI) |
| After 2020 | Thanh et al. (15) | Dawson et al. (21) | Sharifzadeh et al. (22) | Sharma et al. (23) |
| Journal (year) |
Stem Cells Trasl Med 2020 |
J Pediatr 2020 |
Asia Pac Psychiatry 2021 |
Am J Stem Cells 2020 |
| Study design |
Open label BMT repeated within 6 months |
2:1 randomized, placebo-controlled, double-blind (Phase II) |
Randomized controlled trial | Open label non-randomized |
| Patients (n) (gender, age) |
30 (5f/25m; 3-7.4y) |
180 (37f/143m; 2-7y) |
32 (5f/27m; 5-15y) |
254 (31f/223m; 2-34y) |
| Groups | 30 intervention | 56 autologous UCB 63 allogeneic UCB 61 placebo |
14 intervention (plus rehabilitation) 18 control (rehabilitation therapy and risperidone) |
254 intervention (plus neurorehabilitation) |
| SC origin | BM | UCB | BM | BM |
| Application route |
Intrathecal (2x) | Intravenous | Intrathecal (2x) | Intrathecal |
| Follow-up | 6, 12, and 18 months | 6 and 12 months | 6 and 12 months | Mean 7.5 months |
| Safety | No major AE | 84 minor AE 29 placebo 55 UCB 16 infusion reactions 4 placebo 12 UCB 6 serious /moderate AE 3 placebo 3 UCB |
No serious AE No other AEs |
No major AE Efficacy |
| Efficacy | CARS: 50 to 46.5 VABS: 53.6 to 60.5 Improved social communication, language, and daily skills |
Trend towards improvement in the allogenic UCB group (CGI) | Limited clinical efficacy (no differences regarding CARS total score, GARS-II autism index, and CGI global improvement) | Positive change in ISAA and CARS; improved brain metabolism with PET-CT scan in all 86 patients |
ABC, Aberrant Behavior Checklist; AE, adverse event; BM, bone marrow; CARS, Childhood Autism Rating Scale; CGI, Clinical Global Impression scale; EGT, Eye Gaze Tracking of Social Stimuli; EOWPVT-4, Expressive One-Word Picture Vocabulary Test (4th edition); FIM, Functional Independence Measure; f, female; GARS-II, Gillian Autism Rating Scale (2nd edition); ISAA, Indian Scale for Assessment of Autism; m, male; PET-CT, Positron emission tomography; PDDBI, Pervasive Developmental Disorder Behavior Inventory; ROWPVT-4, Receptive One Word Picture Vocabulary Test (4th edition); SBFR, Stanford Binet (5th edition) Fluid Reasoning; SBKN, Stanford Binet (5th edition) Knowledge subtests; sign, significant; SCT, stem cell transplantation; UC, umbilical cord; UCB, umbilical cord blood; VABS-3, Vineland Adaptive Behavior Scales (3rd edition).