Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report

Alexander A. Boucher, Weston Miller, Ryan Shanley, Richard Ziegler, Troy Lund, Gerald Raymond, Paul J. Orchard

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79 Scopus citations


Abstract Background: Metachromatic Leukodystrophy (MLD) is a rare, fatal demyelinating disorder with limited treatment options. Published outcomes after hematopoietic stem cell transplantation (HSCT) are scant and mixed. We report survival and function following HSCT for a large, single-center MLD cohort. Methods: Transplant-related data, survival and serial measures (brain MRI, nerve conduction velocity (NCV), neurologic and neuropsychology evaluations) were reviewed. When possible, parental interviews informed current neurologic status, quality-of-life, and adaptive functioning. Gross motor and expressive functions for late-infantile (LI-MLD) and juvenile (J-MLD) patients were described using previously reported, MLD-specific scales. Results: Forty patients with confirmed MLD have undergone HSCT at our center. Twenty-one (53 %) survive at a median 12 years post-HSCT. Most deaths (n = 17) were treatment-related; two died from disease progression. Survival did not depend upon MLD subtype or symptom status at transplant. LI-MLD patients survive beyond reported life expectancy in untreated disease. Abnormal brain MRI and peripheral nerve conduction velocities (NCV) were common before HSCT. Following transplant, fewer patients experienced MRI progression compared to NCV deterioration. Sixteen LI-MLD and J-MLD survivors were evaluable for long-term gross motor and/or expressive language functioning using existing MLD clinical scoring systems. While most J-MLD patients regressed, the aggregate cohort demonstrated superior retention of function compared to published natural history. Seventeen LI-MLD, J-MLD and adult subtype (A-MLD) survivors were evaluable for long-term adaptive functioning, activities of daily living, and/or cognition. Relative cognitive sparing was observed despite overall global decline. Five sibling pairs (one LI-MLD and four J-MLD), in which at least one underwent transplant in our cohort, were evaluable. Within each familial dyad, survival or function was superior for the treated sibling, or if both siblings were transplanted, for the pre-symptomatic sibling. Conclusions: HSCT is a viable treatment option for MLD, but has significant limitations. Later-onset phenotypes may benefit most from early, pre-symptomatic transplant. Until superior, novel treatment strategies are demonstrated, MLD patients should be carefully considered for HSCT.

Original languageEnglish (US)
Article number313
JournalOrphanet Journal of Rare Diseases
Issue number1
StatePublished - Aug 7 2015

Bibliographical note

Funding Information:
Biostatistical support for this research publication was supported by NIH grants P30 CA77598 and P01 CA65493 utilizing the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number 8UL1TR000114-02. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We gratefully recognize the University of Minnesota Division of Blood and Marrow Transplant at Masonic Children’s Hospital (Minneapolis, MN) for the decades of previous investigators who have laid the foundation for this review to occur. We thank Mrs. Kelly Miettunen and Mrs. Teresa Kivisto for invaluable assistance in logistics for this study. Most of all, we are indebted to the patients and their families who have entrusted our center with their care.

Publisher Copyright:
© 2015 Boucher et al.


  • Bone marrow transplantation
  • Hematopoietic stem cell transplantation
  • Metachromatic leukodystrophy
  • Umbilical cord blood transplantation


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