Table 3.
Summary of clinical outcomes of HSCT
| Patient | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Follow-up period after HSCT (years) | 10.4 | 6.7 | 4.9 | 4.6 | 3.0 | 2.7 | 2.1 | 1.5 | 0.7 | 0.5 | 0.4 | 0.3 |
| Neurological outcome | Stable for 10.4 years. Dysarthria improved, lower limb weakness progressed graduallya | Stable for 6.7 years | Stable for 4.9 years | Stable for 4.6 years. Dysarthria and dysphagia improved, lower limb weakness slightly progressed till 1 month after HSCT | Stable for 3.0 years. Dysarthria improved, truncal ataxia slightly progressed till 9 months after HSCT | Stable for 2.7 years | Stable for 2.1 years. Gait speed decreased till 8 months after HSCTb | Stable for 1.5 years | Stable for 0.7 years. Ataxia and lower limb weakness slightly progressed till 2 months after HSCT | Stable for 0.5 years.Small voice and pyramidal weakness substantially improved, dysphagia, deep sensation and bowel disturbance improved | Stable for 0.4 years. Decreased superficial sensation spread to the trunk/upper limbs and right dominant spasticity of lower limbs slightly progressed till 2 months after HSCT | Stable for 0.3 years. Pyramidal weakness and bladder disturbance slightly progressed till 2 months after HSCT |
| EDSS/Barthel Index/ALD-DRS (months after HSCT) | 8.5/55/II (95) | 2.0/100/I (79) | 3.5/90/I (12) | 7.0/40/III (26) | 6.5/85/II (13) | 6.0/100/II (24) | 6.5/90/II (24) | 3.0/90/II (14) | 6.5/85/III (3) | 8.5/15/III (1) | 6.0/85/II (2) | 5.0/85/II (2) |
| C26:0/C22:0 after HSCT (normal range 0.003–0.006) | 0.014 | 0.028 | 0.016 | 0.021 | 0.019 | 0.032 | 0.016 | 0.023 | 0.022 | 0.033 | 0.019 | N.T.c |
| Percentage of DNAs from the recipient (months after HSCT)d | 0.03% (95) | <0.01% (50) | 0.06% (12) | 0.06% (26) | 0.42% (5) | 0.08% (11) | 0.05% (9) | 0.43% (2) | 0.12% (2) | 0.17% (1) | 0.62% (2) | N.T.c |
| MRI findings | ||||||||||||
| Brain MRI after HSCT | Reduction in size of lesions of auditory pathway and splenium of corpus callosum. Atrophic changes in cerebellum and brainstem | Reduction in size of temporal and cerebellar lesions | Reduction in size of brainstem lesions | Reduction in size of pyramidal tract and cerebellar lesions. Atrophic changes in cerebellum and brainstem | Stabilization of enlargement of white matter lesions. Atrophic changes in cerebellum and brainstem | Stabilization of enlargement of white matter lesions | Reduction in size of frontal, parietal, occipital and temporal lesions | Stabilization of enlargement of white matter lesions | Reduction in size of pyramidal tract in brainstem, middle cerebellar peduncles and cerebellar lesions | Reduction in size of pyramidal tract and auditory pathway lesions | Stabilization of enlargement of white matter lesions | Stabilization of enlargement of white matter lesions |
| Loes scores before HSCT | 11 | 3 | 6 | 4 | 6 | 2 | 7.5 | 6.5 | 5.5 | 8.5 | 5 | 13 |
| Loes scores after HSCT (years after HSCT) | 12 (3.1) | 1.5 (6.7) | 2 (4.4) | 5 (3.1) | 7 (1.1) | 2 (1.9) | 5.5 (2.0) | 6.5 (1.2) | 5 (0.5) | 8.5 (0.4) | 5 (0.2) | 13 (0.1) |
| Gd enhancement on brain MRI before HSCT | Enhanced | Enhanced | Enhancede | Enhanced | Enhanced | Not enhanced | Enhanced | Enhanced | Enhanced | Enhanced | Not enhanced | Enhanced |
| Gd enhancement on brain MRI after HSCT (months after HSCT) | Not enhanced (37) | Not enhanced (80)f | Not enhanced (12) | Not enhanced (12) | Not enhanced (13) | Not enhanced (1) | Not enhanced (1) | Not enhanced (14) | Not enhanced (6) | Obscuredg (1) | Not enhanced (3) | Obscuredg (2) |
N.T. = not tested; ALD-DRS = X-linked ALD-disability rating scale, EDSS = expanded disability status scale.
Owing to lower limb weakness, patients’ activities of daily living decreased. Patient 1 spends a lot of time in a seated position, but he can move to his portable toilet with a grab bar.
He encountered a traffic accident with a right tibiofibular fracture 1.4 years after HSCT, which impaired his gait.
We have not measured the VLCFA levels in plasma sphingomyelin and performed chimerism analysis using peripheral white blood cells for Patient 12 because HSCT has been conducted very recently. The fluorescence in situ hybridization analysis of bone marrow cells a month after HSCT in Patient 12 showed that the percentage of cells from the recipient with respect to that from the donor was 0.5%.
The percentages of the DNAs derived from the recipients with respect to those from their donors in peripheral white blood cells after HSCT.
The auditory pathway in the brainstem was Gd-enhanced 9.5 months before HSCT, but Gd enhancement was not obvious 0.8 months before HSCT.
Gd-enhanced lesions on brain MRI became obscure 3.5 months after HSCT and undetected 19 months after HSCT.
Gd-enhanced lesions on brain MRI became obscure but did not completely disappear, presumably because the follow-up period of brain MRI was short (around 1–2 months) after HSCT.