Allogeneic haematopoietic stem cell transplantation with myeloablative conditioning for adult cerebral X-linked adrenoleukodystrophy

  • Nils Waldhüter
  • Wolfgang Köhler
  • Philipp G. Hemmati
  • Christian Jehn
  • Rudolf Peceny
  • Giang L. Vuong
  • Renate Arnold
  • Jörn-Sven KühlEmail author
Original Article


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.


X-linked adrenoleukodystrophy Adult cerebral ALD Haematopoietic stem cell transplantation Myeloablative conditioning Magnetic resonance imaging Internal capsule 



Adult ALD Clinical Score


Adult cerebral ALD






Anti-thymocyte globulin


Bone marrow


Childhood cerebral ALD


Kurtzke Expanded Disability Status Scale


Granulocyte colony-stimulating factor


Graft-versus-host disease


Haematopoietic stem cell transplantation


Magnetic resonance imaging


Peripheral blood stem cells


Very long chain fatty acids


X-linked ALD



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.

Supplementary material

10545_2018_241_MOESM1_ESM.doc (44 kb)
ESM 1 (DOC 44 kb)


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Copyright information

© SSIEM 2018

Authors and Affiliations

  1. 1.Department Hematology, Oncology and TumorimmunologyCharité Campus Virchow-KlinikumBerlinGermany
  2. 2.Department NeurologyUniversitätsklinikum LeipzigLeipzigGermany
  3. 3.Department Oncology/Hematology/SCTKlinikum OsnabrückOsnabrückGermany
  4. 4.Department Pediatric Oncology/Hematology/SCTCharité Campus Virchow-KlinikumBerlinGermany
  5. 5.Department Pediatric Oncology/Hematology/HemostasealogyUniversitätsmedizin LeipzigLeipzigGermany

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