MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis

MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG

This single-institution, phase II study is designed to test the ability to achieve donor hematopoietic engraftment while maintaining low rates of transplant-related mortality (TRM) using busulfan- and fludarabine-based conditioning regimens with busulfan therapeutic drug monitoring (TDM) for patients with various inherited metabolic disorders (IMD) and severe osteopetrosis (OP).

Inclusion Criteria:

• 0 through 55 years of age

• Adequate graft available

• Adequate organ function

• Eligible Diseases:

  • Mucopolysaccharidosis Disorders:

    • MPS IH (Hurler syndrome)
    • MPS II (Hunter syndrome) if the patient has no or minimal evidence of symptomatic neurologic disease but is expected to have a neurologic phenotype
    • MPS VI (Maroteaux-Lamy syndrome)
    • MPS VII (Sly syndrome)

  • Glycoprotein Metabolic Disorders:

    • Alpha mannosidosis
    • Fucosidosis
    • Aspartylglucosaminuria

  • Sphingolipidoses and Recessive Leukodystrophies:

    • Globoid cell leukodystrophy
    • Metachromatic leukodystrophy
    • Niemann-Pick B patients (sphingomyelin deficiency)
    • Niemann-Pick C subtype 2

  • Peroxisomal Disorders:

    • Adrenoleukodystrophy with cerebral involvement
    • Zellweger syndrome
    • Neonatal Adrenoleukodystrophy
    • Infantile Refsum disease
    • Acyl-CoA-Oxidase Deficiency
    • D-Bifunctional enzyme deficiency
    • Multifunctional enzyme deficiency
    • Alpha-methylacyl-CoA Racmase Deficiency (AMACRD)
    • Mitochondrial Neurogastrointestingal Encephalopathy (MNGIE)

  • Severe Osteopetrosis (OP)

  • Hereditary Leukoencephalopathy with axonal spheroids (HDLS; CSF1R mutation)

  • Other Inherited Metabolic Disorders (IMD): Patients will also be considered who have other life-threatening, rare lysosomal, peroxisomal or other similar inherited disorders characterized by white matter disease or other neurologic manifestations for which there is rationale that transplantation would be of benefit, such as certain patients with Wolman's disease, GM1 gangliosidosis, I-cell disease, Tay-Sachs disease, Sandhoff disease or others.

  • Voluntary written consent

Exclusion Criteria:

• Pregnancy - menstruating females must have a negative serum or urine pregnancy test within 14 days of study treatment start
• Prior myeloablative chemotherapy exposure within 4 months of the start of conditioning on this protocol (patients excluded for this reason may be eligible for other institutional protocols)
• Uncontrolled bacterial, fungal or viral infections including HIV (including active infection with Aspergillus or other mold within 30 days)