Abstract 9
Introduction
Administration of cellular therapy products carries a risk of infusion reaction. Reactions are typically transient, but range in severity from mild (eg, rash, congestion) to severe (eg, anaphylaxis). Data reported in the literature indicate a low incidence (<10%) of infusion reactions, with variability across studies of limited sample sizes. We reviewed a large sample of children who received umbilical cord blood (CB) infusions to describe the incidence and severity of infusion reactions.
Objective
The objective of this study was to describe infusion reactions in children with neurological conditions receiving autologous or sibling CB infusions under an Expanded Access Protocol (EAP) at Duke University.
Methods
Through an EAP (IND# 15949), children with autism spectrum disorder (ASD), cerebral palsy (CP), and related brain injuries undergo CB infusion with autologous or sibling (≥3/6 human leukocyte antigen [HLA] match) CB. Children are premedicated with IV diphenhydramine and methylprednisolone 15‐30 minutes prior to infusion. CB is thawed, washed, and infused peripherally over ∼10 minutes. Blood pressure and oxygen saturation are monitored throughout, and emergency medications are available at the bedside. Data regarding infusion reactions in this population were obtained from a REDCap (Research Electronic Data Capture, hosted at Duke University) database and clinical records.
Results
Between November 2017 and July 2020, 385 children (235 with ASD, 104 with CP, and 46 in the “other related brain injuries” group) treated with CB (219 autologous, 166 sibling) experienced 38 (9.9%) infusion reactions. Reactions were more common in children with ASD (14%), with no difference between autologous and sibling infusions. Most reactions were mild (37% grade 1, 42% grade 2), commonly consisting of cough and/or sneezing and less commonly of rash or bronchospasm. Two children who experienced more severe reactions were hospitalized for observation, including one for anaphylaxis requiring treatment with epinephrine. Treatment of infusion reactions typically included administration of additional Benadryl (91%), steroids (46%), and bronchodilators (35%), as necessary. Most (66%) infusions were able to be completed, and all reactions resolved completely with treatment (Table 1).
Table 1.
Patient, umbilical cord blood unit, and treatment characteristics
| Characteristic | Autologous (n = 21) | Sibling (n = 17) | Total (n = 38) |
|---|---|---|---|
| Patient characteristics | |||
| Age, median (range) | 6.83 (2.08‐9.75) | 6.75 (4.0‐15.5) | 6.8 (2.1‐15.5) |
| Diagnosis | |||
| Autism spectrum disorder | 20 (95.2%) | 12 (70.5%) | 32 (86.5%) |
| Cerebral palsy | 1 (4.8%) | 5 (29.5%) | 6 (15.7%) |
| Known allergies | |||
| Medication | 4 (19%) | 4 (23.5%) | 8 (21%) |
| Food | 9 (42.8%) | 5 (29.4%) | 14 (36.8%) |
| Cord blood characteristics | |||
| Thawed TNCC (×107/kg), median (range) | 2.4 (0.9‐4.5) | 2.6 (1.01‐5.6) | 2.6 (0.9‐5.6) |
| HLA match | |||
| 6/6 | 21 (100%) | 7 (41.2%) | 28 (73.7%) |
| 4/6 | – | 3 (17.6%) | 3 (7.9%) |
| 3/6 | – | 7 (41.2%) | 7 (18.4%) |
| Infusion successfully completed | 17 (80.9%) | 8 (47.1%) | 25 (65.7%) |
| Infusion reaction characteristics | |||
| CTCAE Grade | |||
| 1 | 11 (52.4%) | 3 (17.6%) | 14 (36.8%) |
| 2 | 5 (23.8%) | 11 (64.7%) | 16 (42.1%) |
| 3 | 5 (23.8%) | 3 (17.6%) | 8 (21%) |
| 4 | 0 (0%) | 0 (0%) | 0 (0%) |
| Symptoms | |||
| Allergy/hypersensitivity | 20 (95.2%) | 17 (100%) | 37 (97.4%) |
| Tachycardia | 2 (9.5%) | 3 (17.6%) | 5 (13.5%) |
| Hypotension | 0 (0%) | 2 (11.8%) | 2 (5.3%) |
| Hypoxia | 3 (14.3%) | 6 (35.3%) | 9 (23.7%) |
| Rash | 2 (9.5%) | 3 (17.6%) | 5 (13.5%) |
| Nausea/Vomiting | 0 (0%) | 2 (11.8%) | 2 (5.3%) |
| Treatment | |||
| IV diphenhydramine | 19 (90.5%) | 15 (88.2%) | 34 (89.5%) |
| IV methylprednisolone | 5 (23.8%) | 10 (58.8%) | 15 (39.5%) |
| Inhaled albuterol | 5 (23.8%) | 8 (47%) | 13 (34.2%) |
| Oxygen | 2 (9.5%) | 3 (17.6%) | 5 (13.2%) |
| Other steroid | 2 (9.5%) | 3 (17.6%) | 5 (13.2%) |
| Epinephrine | 0 | 1 (5.9%) | 1 (2.6%) |
Discussion
While CB infusion is generally safe, there is a real risk of infusion reactions requiring additional medical treatment. With prompt, appropriate treatment, recovery is rapid and complete. As such, CB infusions should be attended by trained professionals experienced in the treatment of acute infusion reactions.