Brain-sparing cord blood transplantation for the borderline stage of adrenoleukodystrophy

• Published in: Molecular Genetics and Metabolism Reports Vol. 28; p. 100778
• Main Authors: Yada, Yutaro, Torio, Michiko, Koga, Yuhki, Yamashita, Fumiya, Ichimura, Takuya, Eguchi, Katsuhide, Ishimura, Masataka, Mushimoto, Yuichi, Hiwatashi, Akio, Sasazuki, Momoko, Kira, Ryutaro, Sakai, Yasunari, Ohga, Shouichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2021; Elsevier BV; Elsevier
• Subjects: Adrenoleukodystrophy; Biology (General); Brain-sparing irradiation; Case Report; Hematopoietic cell transplantation; Loes score; Medicine (General); QH301-705.5; R5-920; Reduced-intensity conditioning; HDC; Brain-sparing irradiation; GVHD; Hematopoietic cell transplantation; ASD; Adrenoleukodystrophy; CBT; VLCFA; Loes score; HCT; Reduced-intensity conditioning; ALD; HLA; GVHD, graft failure and graft-versus-host disease; HLA, human leukocyte antigen; ALD, Adrenoleukodystrophy; ASD, autism spectrum disorder; HDC, hydrocortisone; VLCFA, very long-chain saturated fatty acids; HCT, hematopoietic cell transplantation; CBT, cord blood transplantation
• ISSN: 2214-4269; 2214-4269
• DOI: 10.1016/j.ymgmr.2021.100778

Adrenoleukodystrophy (ALD) is an X-linked disorder characterized by rapidly progressive deterioration of neurocognitive functions and premature death. In addition to the difficulty in identifying the earliest signs of ALD, treatment-associated exacerbation of neurological symptoms has been an obstacle to achieve successful hematopoietic cell transplantation (HCT) for affected children. We report a 9-year-boy with ALD. He presented with impairment in social skills compatible to the diagnosis of autism spectrum disorder from 3 years of age. He showed progressive strabismus, slurred speech and dysmetria at 6 years of age. The head MRI showed symmetrical T2-hyperintense lesions in the occipital white matters with a gadolinium enhancement, which extended to the internal capsules. The Loes score was thus calculated as 13. Very-long-chain-fatty-acids were increased to 1.800 (C24:0/C22:0) and 0.077 (C26:0/C22:0) in leukocytes. Sanger sequencing confirmed the pathogenic variant in ABCD1 (NM_000033.4:p.Gly512Ser). After multidisciplinary discussions over the treatment options, we performed a cord blood HCT with a reduced intensity conditioning (fludarabine, melphalan and brain-sparing total body irradiation). He was fully recovered with >90% chimerism of donor leukocytes at 55 days after HCT. He experienced three times of generalized seizures after discharge, that has been well controlled for 2 years without other complications or neurocognitive deteriorations. For patients with ALD on a borderline indication for HCT, brain-sparing irradiation might be an alternative option in reduced intensity conditioning. Careful decision-making process and tailored conditioning are critical for the successful outcome of HCT for children with ALD. •Therapeutic strategies remain to be established for adrenoleukodystrophy.•Multidisciplinary discussions are necessary for making a decision of treatment.•A 6-year-old boy achieved a successful engraftment after the transplantation.•The brain-sparing method might provide favorable outcomes for adrenoleukodystrophy.