Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism

Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Hematopoietic Cell Transplantation

The primary objective of this clinical trial is to evaluate the ability to achieve and sustain donor engraftment in patients with lysosomal and peroxisomal inborn errors of metabolism undergoing hematopoietic stem cell transplantation (HCT).

This has been an ongoing area of interest by our group at the Univ. of Minnesota, but this is a new protocol to take the place of several older protocols. While survival has been very good on the prior protocols over the past decade, incomplete engraftment has remained somewhat problematic. Therefore, we have modified the preparative regimen somewhat to increase engraftment by replacing anti-thymocyte globulin (ATG) with Campath-1H, a drug that is more immune suppressive. In addition, we have modified the supportive care regimen. Based on this, we will monitor levels of an anti-oxidant therapy (N-acetylcysteine) and biomarkers of inflammation and oxidative stress for the families that consent to these research studies.

Inclusion Criteria:

• Mucopolysaccharidosis (MPS) Disorders:

  • MPS IH (Hurler syndrome)
  • MPS-VI (Maroteaux-Lamy syndrome)
  • MPS VII (Sly syndrome).

• Glycoprotein metabolic disorders:

  • Alpha mannosidosis
  • Fucosidosis
  • Aspartylglucosaminuria

• Sphingolipidoses and Recessive Leukodystrophies: Presymptomatic patients with globoid cell leukodystrophy (GLD, also known as Krabbe disease) and metachromatic leukodystrophy (MLD) will be eligible for treatment on this protocol. White matter disease by magnetic resonance imaging (MRI) alone is not an exclusion if the patient is asymptomatic.

• Peroxisomal Disorders: Presymptomatic patients with inherited peroxisomal disorders associated with of very long chain fatty acids (VLCFA) elevation, identified by family history or laboratory testing (including neonatal screening), are eligible for this protocol. White matter disease by MRI alone is not an exclusion if the patient is asymptomatic.

• Other Inherited Diseases of Metabolism:

  • Wolman syndrome (acid lipase deficiency)
  • Niemann-Pick B patients (sphingomyelin deficiency)
  • Niemann-Pick C subtype 2

• Donor Availability: Patients considered for transplantation must have a sufficient graft as based on current criteria of the University of Minnesota Blood and Marrow Transplantation Program: Priority will be as follows, although in circumstances in which timing is of the essence, cord blood grafts may be chosen over an unrelated graft, despite the priority listed above.

• Multidisciplinary Evaluation: Patients will be eligible for transplantation only after they are seen and evaluated by members of the Inherited Metabolic and Storage Disease Program (IMSD) team, and the team has offered transplantation to the patient/family.

Exclusion Criteria:

• Symptomatic patients with peroxisomal or lysosomal disorders are excluded but may be considered for other treatment protocols.

• Major organ dysfunction. Evidence of major organ impairment, including:

  • Cardiac: left ventricular ejection fraction <40%
  • Renal: serum creatinine >2.5 x normal for age
  • Hepatic: total bilirubin >3 x normal, or Alanine transaminase (ALT) > 3 x normal
  • Pulmonary: requirement for continuous oxygen supplementation

• Pregnancy

• Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology

• Patients >21 years of age.