ObjectiveTo investigate characteristics of children with X-linked adrenoleukodystrophy (X-ALD) and the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT).
MethodsFrom February 2015 to December 2018, a total of 3 children with X-ALD admitted to the Children′s Hospital of Soochow University were selected as the research subjects. According to the order of admission time, 3 cases were numbered as child 1, 2 and 3. They were all male. Their ages were 7 years and 6 months, 9 years and 7 months, 8 years and 10 months, respectively. All the 3 cases were accompanied with cerebral adrenoleukodystrophy (CALD) symptoms. Clinical data of 3 cases with X-ALD were collected. All the children were pretreated with modified fludarabine+ busulfan+ cyclophosphamide regimen. Child 1, 2 received double umbilical cord blood transplantation (UCBT) and child 3 received haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Clinical features and the curative effect of allo-HSCT in children with X-ALD were retrospectively analyzed. The procedure followed in this study was in accordance with the requirements of theWorld Medical Association Declaration of Helsinkirevised in 2013.
Results① After admitted, head MRI examination of child 1 showed that the white matter of bilateral parietal occipital lobe, splenium of corpus callosum and part of brainstem were involved. Neurological function score was 0 and Loes score was 8. Head MRI of child 2 showed that the lateral midbrain, bilateral dorsal thalamus and splenium callosum were involved. Neurological function score was 0 and Loes score was 15. Head MRI showed bilateral cerebral peduncle and temporal parietal occipital lobe involvement in child 3. The child had aphasia and epileptic seizures when he was admitted to hospital. The muscle tension of both lower limbs and left upper limbs was significantly increased. Neurological function score was 8 and Loes score was 6. All of the 3 children were diagnosed as X-ALD. Child 2 and 3 were not suitable for allo-HSCT according to above scores, but their parents still strongly demanded transplantation. ② After pretreatment, all the children successfully completed allo-HSCT. Infused mononuclear cell counts were 10.74×108/kg, 20.73×108/kg and 32.22×108/kg, respectively. Infused CD34+cell counts were 10.26×106/kg, 20.32×106/kg and 32.27×106/kg, respectively. Time to neutrophil implantation were 20, 12, 9 d, and time to platelet implantation were 43, 14, 11 d, respectively. ③ allo-HSCT in all 3 cases were successfully. Results of short tandem repeats (STR) monitoring of child 1 showed that he was in complete implantation state at the end of follow-up. No GVHD was present in child 1, and chronic GVHD (cGVHD) in skin was present in child 2. After oral methotrexate treatment, the symptoms were improved. Two months after transplantation, acute GVHD (aGVHD) occurred in the intestine of child 3, which improved after anti-rejection therapy. Epstein-Barr virus (EBV) infection occurred in child 3 after transplantation, and was improved after treatment with acyclovir and foscarnet sodium. ④ After treatment, the results of head MRI showed that the disease had no progress, and there was no clinical manifestation of nervous system damage in child 1. Condition of child 2 was stable 3 months after transplantation. Results of head MRI examination indicated no disease progression and no clinical neurological damage. Later, due to family financial reasons, regular follow-up of child 2 was not possible. And the child died of sudden infection 12 months after transplantation. Child 3 suffered from further brain damage, repeated convulsions, and then failed to maintain spontaneous breathing. Finally, he died 4 months after transplantation due to sepsis, pulmonary infection and respiratory failure.
ConclusionsAllo-HSCT can prevent the progressive symptoms of CALD in children with X-ALD with better neurological function score and Loes score. It is an effective treatment for X-ALD to find a suitable matching donor in time after early diagnosis and carry out allo-HSCT as soon as possible. However, this study is only a retrospectively clinical analysis of 3 children, which needs to be further verified the efficacy and safety of allo-HSCT for X-ALD children by large sample and prospective study.
