Elsevier

Seminars in Hematology

Volume 47, Issue 1, January 2010, Pages 59-69
Seminars in Hematology

Transplant Outcomes in Mucopolysaccharidoses

https://doi.org/10.1053/j.seminhematol.2009.10.008Get rights and content

The mucopolysaccharidoses (MPSs) are inherited metabolic disorders (IMDs) caused by single-gene defects leading to progressive cellular accumulation of glycosaminoglycans (GAGs) and damage to multiple organs, including the central nervous, musculoskeletal, cardiorespiratory, and other systems. Hurler syndrome (MPS IH), the most severe form, is the prototypical model. Enzyme replacement therapy (ERT), available for MPS I, II, and VI, is beneficial in some patients. However, ERT does not improve neurocognitive function because of its inability to cross the blood-brain barrier. In contrast, allogeneic hematopoietic stem cell transplantation (HSCT) allows donor-derived, enzyme-producing cells to migrate to the brain and other organs to provide permanent enzyme therapy and thus help somatic organs, improve neurocognitive function and quality of life, and prolong survival, particularly when performed early in the course of the disease. Bone marrow has been the graft source in the past. However, in the last 5 years many patients have been treated with unrelated donor (URD) umbilical cord blood transplant (UCBT), allowing rapid and increased access to transplantation with favorable outcomes. This review describes published and our institutional clinical experiences, discusses the current status of the field, and provides therapy guidelines for patients with MPS.

Section snippets

HSCT for Hurler Syndrome (MPS IH)

Continuing improvement in the overall outcomes following HSCT and 25 years of experience in HSCT for Hurler syndrome points to greater familiarity and acceptance of this form of therapy.24, 26 Meanwhile transplant complications and consequent morbidity and mortality have decreased over the years. In addition, the use of cord blood as a donor source has improved access, allowed faster transplantation, and increased donor chimerism and enzyme levels. While these gains are encouraging, many

HSCT for Other Mucopolysaccharidoses

Compared to Hurler syndrome, the overall experience in the use of HSCT for treatment of other MPSs (II, III, IV, VI, and VII) is very limited (Table 1). Subtypes of MPS have many similarities yet significant clinicopathologic differences making them distinct enough to have differential outcomes after HSCT. Undoubtedly, the scientific basis for effectiveness of HSCT across MPS spectrum remains the same. However, there may be individual differences in the kinetics of cellular migration,

Conclusions

Despite their inherent limitations, HSCT and ERT are the only therapies that have been shown to provide benefit in MPS patients. HSCT involves early mortality risks and later morbidity but offers a chance for a life-time supply of donor-derived enzymes to the various organs and tissues, including, most importantly, the CNS. Thus HSCT alone is able to provide neurological and cognitive benefits. There is general consensus that the earlier a patient is diagnosed and treated, the better their

Transplant Guidelines

  • 1

    Patients should be evaluated expeditiously at a center familiar with transplantation for inherited metabolic disorders. HLA typing of the patient and family should be performed. Those patients found to be suitable candidates for HSCT should be evaluated and transplanted quickly to derive maximum benefit.

  • 2

    All patients, regardless of therapy utilized, need comprehensive evaluations for increased intracranial pressure, hearing loss, cardiac disease, neurocognitive and neurodevelopmental status, and

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