Results
febrile seizure, nausea, pneumonia, fever, seizure, seizures, Seizure, bronchopneumonia, cough, SAEs, bronchitis
FEBRILE SEIZURE, PNEUMONIA, UPPER RESPIRATORY INFECTION, GROUP B, PARTIAL SEIZURE, EVENT, BRONCHOPNEUMONIA, BRONCHITIS, EVENTS, AFEBRILE SEIZURE, INFLUENZA
Among the 88 children who completed the previous trial, 76 agreed to participate in this extension study without differences in patient number among the four groups. Although all the participants received the same intervention regardless of their initial allocation this time, the groups in the previous trial remained the same for analysis. After receiving the second intervention, seven children were excluded for efficacy assessments during the study period due to refusal of follow-up visits while they were connected for monitoring (2 from Group A, 1 from Group B, 2 from Group C, and 2 from Group D). Finally, sixty-nine children (4.29 ± 1.28 years, M:F = 34:35) in Group A (No significant differences were found between the four groups in extension baseline (T15) clinical characteristics except for the GMFCS distribution with more severely involved patients in Group D. No other differences were found in the extension baseline (T15) scores for functional measures, administered UCB immune compatibility, and serum cyclosporine levels drawn on the day and 3 days after the UCB infusion (Table Demographic and baseline participant characteristics (n = 69)Values represent number of patients unless otherwise noted. No baseline characteristics were significantly different between four groups (To evaluate the safety of UCB therapy, AEs were monitored. Among the reports, four AEs in two patients (S62: one cough event and one nausea event, immediately after UCB infusion, and S76: one fever event and one pneumonia event, the day after the intervention) were regarded as possibly related to the intervention. In the case of S62, the symptoms disappeared within a few minutes with pheniramine injection, and the vital signs were stable without deviation from the normal range. Patient S76 had taken medication for upper respiratory infection until a few days before the treatment. Although his initial CRP level at 2 days before the UCB infusion was 1.4 mg/dL, he undertook the treatment since his CRP level decreased to 0.37 mg/dL on the day of infusion without any further management. However, he had a fever up to 38.6 °C on the next day and showed elevation of CRP up to 7.9 mg/dL. Under the impression of bronchopneumonia on chest X-ray, he started and continued antibiotic treatment for four days. All the subjects recovered from the AEs. Eleven serious AEs (SAEs) from five patients were reported during this study period, which were unlikely to be related to the intervention. All SAEs that occurred were not regarded as related to the intervention. Seizure attacks were the most frequent, with six events in four patients (two patients had events twice in a separate period), including three events of febrile seizure, which were also designated as three events of fever among the SAEs. Of these three febrile seizure events, one was caused by influenza; thus, this event was also designated as one influenza event among the SAEs. Regarding three seizure attacks without fever, two events occurred in one patient (S27) who already had a history of seizures and was under medication. The other patient (S07) showed a partial seizure wave on electroencephalography, which was conducted before UCB infusion and was not medicated afterwards by the decision of a paediatric neurologist. The other case was one with bronchitis. Of the fifteen seizure events among all AEs, there was only one case (S07) of newly developed attack, which is described in the SAE section (Additional file Regarding efficacy, which was assessed compared to the extension baseline (T15), the participants showed improvements in their GMFM-66, GMPM, and BSID-II scores at the follow-up functional evaluation time points (Changes in functional scores at each time point from the baseline (T15). Each are changes of (Changes of GMFM-66 during each interval between time pointData are shown as mean ± standard error. Each are changes of GMFM-66 compared to the baselines of first (T0) and second trial (T15), at 3 (T18), 6 (T21), and 12 (T27) months after 2nd intervention. Also, the changes between T12 and T0 are shown to show the reduced gap as each patient aged. †Group A (n = 16) received UCB and EPO, Group B (n = 19) received UCB and placebo EPO, Group C (n = 16) received placebo UCB and EPO, and Group D (n = 18) received placebo UCB and placebo EPO at the beginning of the 1st trial (T0), and all the groups were equally treated with UCB at the beginning of the 2nd trial (T15). *shows significant changes (Further intergroup comparison analyses, including an efficacy assessment from the starting point of T0 to the last visit T27 and a subgroup comparison according to severity, revealed a meaningful finding. Among 41 children with severe impairments at levels of GMFCS IV or V, Group A showed meaningful improvement in GMPM from T0 to T18 compared to Group D (Motor function improvement in children with severe impairments. Changes in (In the present study, we again found significance of the cell number in UCB therapy, as had repeatedly appeared in previous trials [Changes in functional scores at each time point from the baseline (T15) depending on total nucleated cell count. The patients were divided into two groups depending on the amount of total nucleated cell (TNC) they were given. Compared to the median TNC (4.4 × 10In this report, the authors present serial scores of each patient’s GMFM-66 according to age depicted on the reference graph [