Allogeneic haematopoietic stem cell transplantation with myeloablative conditioning for adult cerebral X-linked adrenoleukodystrophy
The adult cerebral form of X-linked adrenoleukodystrophy (ACALD), an acute inflammatory demyelinating disease, results in a rapidly progressive neurodegeneration, typically leading to severe disability or death within a few years after onset. We have treated 15 men who had developed ACALD with allogeneic haematopoietic stem cell transplantation (HSCT) from matched donors after myeloablative conditioning with busulfan and cyclophosphamide. All patients engrafted and 11 survived (estimated survival 73 ± 11%), eight with stable cognition and seven of them with stable motor function (estimated event-free survival 36 ± 17%). Death after transplantation occurred within the first year after HSCT and was caused either primarily by infection (n = 3) or due to disease progression triggered by infection (n = 1). Patients with minor myelopathic symptoms (n = 4) or with no or mild cerebral symptoms pre-transplant (n = 7) had an excellent outcome. In contrast, no patient with major neurological symptoms associated with an extensive involvement of pyramidal tract fibres in the internal capsule (n = 5) survived without cognitive deterioration. Notably, early leukocyte recovery was associated with dismal outcome for yet unknown reasons. All ten tested survivors showed a reduction of plasma hexacosanoic acid (C26:0) in the absence of Lorenzo’s oil. Over time, the event-free survival could be improved from 2 out of 8 patients (25%) before 2013 to 5 out of 7 patients (71%) thereafter. Therefore, allogeneic HSCT appears to be a suitable treatment option for carefully selected ACALD patients when transplanted from matched donors after myeloablative, busulfan-based conditioning.
KeywordsX-linked adrenoleukodystrophy Adult cerebral ALD Haematopoietic stem cell transplantation Myeloablative conditioning Magnetic resonance imaging Internal capsule
Adult ALD Clinical Score
Adult cerebral ALD
Childhood cerebral ALD
Kurtzke Expanded Disability Status Scale
Granulocyte colony-stimulating factor
Haematopoietic stem cell transplantation
Magnetic resonance imaging
Peripheral blood stem cells
Very long chain fatty acids
We are indebted to PD Dr. M. Nagy, Berlin, for the laboratory expertise in performing DNA chimerism and to Dr. rer. nat. D. Hunneman, Göttingen, for measuring VLCFA in plasma.
We thank the non-profit organisations Myelin Project, Germany, ELA Germany, StopALD, USA, and ALD Charity, Switzerland for encouraging and supporting patients and families.
No specific funding to report.
Compliance with ethical standards
Conflict of interest
Wolfgang Köhler, Christian Jehn and Renate Arnold have no conflict of interest.
Nils Waldhüter has received a travel grant from Pfizer.
Philipp G. Hemmati has received a travel grant from Neovii.
Rudolf Peceny has received a travel grant from Sanofi.
Giang L. Vuong has received travel grants from Celgene and Gilead.
Jörn-Sven Kühl has received honoraria from bluebird bio and a travel grant from Neovii.
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