Stem Cell Transplantation for Hurler
Condition: Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Mannosidosis; Mucolipidosis Type II (I-cell Disease)
MeSH terms: Mucolipidoses; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mannosidase Deficiency Diseases; alpha-Mannosidosis; Mucopolysaccharidosis VI
Intervention: Stem Cell Transplant; Busulfan, Cyclophosphamide, ATG
Intervention description: The purpose of hematopoietic cell transplantation is to introduce hematopoietic cells from a normal donor that contains the enzyme able to get rid of the substances that have accumulated in the body of patients with storage diseases. Hematopoietic cells can come from bone marrow, peripheral blood (i.e., the blood circulating in our body's blood vessels) or umbilical cord blood (i.e. blood taken from the umbilical cord after a baby is born and umbilical cord is cut).; Prior to transplantation, subjects will receive BUSULFAN intravenously (IV) via the Hickman line twice daily for 4 days, CYCLOPHOSPHAMIDE intravenously via the Hickman line once a day for 4 days, and ANTI-THYMOCYTE GLOBULIN IV via the Hickman line twice daily for three days before the transplant. These three drugs are being given to help the new marrow "take" and grow. METHYLPREDNISOLONE will be given as a pre-medication for the ATG.
Intervention MeSH terms: Cyclophosphamide; Busulfan; Thymoglobulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Healthy volunteers: No
Keywords: stem cell transplant; storage disease; errors of metabolism

Summary:

      The purpose of this study is to determine the safety and engraftment of donor hematopoietic
      cells using this conditioning regimen in patients undergoing a hematopoietic (blood forming)
      cell transplant for Hurler syndrome, Maroteaux Lamy syndrome, Mannosidosis, or I-cell
      disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with Mucopolysaccharidosis, type I (e.g., Hurler syndrome), Maroteaux-Lamy
             syndrome (MPS VI), Alpha Mannosidosis, or mucolipidosis type II (I-cell disease) who
             have an HLA-identical or mismatched (at 1 antigen) related marrow, PBSC, or cord blood
             donor.

          -  Patients with Mucopolysaccharidosis, type I, Maroteaux-Lamy syndrome (MPS VI), Alpha
             Mannosidosis, or mucolipidosis type II (I-cell disease) who have an HLA-identical or
             HLA-1 antigen mismatched unrelated marrow, PBSC, or HLA-0-2 antigen mismatched
             umbilical cord blood donor.

          -  Patients with MPS type I, Maroteaux Lamy Syndrome (MPS VI), or mucolipidosis type II
             (I-cell disease) will have a mental developmental index within two standard deviations
             of the normal mean, as best as can be determined using Bayley scales of infant
             development or other standardized testing, recognizing that these may be affected by
             speech and/or hearing impairment.

          -  Adequate organ function:

          -  Cardiac: ejection fraction >40%; no decompensated congestive heart failure or
             uncontrolled arrhythmia

          -  Renal: serum creatinine <2.0 mg/dl

          -  Hepatic: total bilirubin <3x Upper limits of normal transaminases < 5.0 x Upper limits
             of normal

          -  Signed consent.

        Exclusion Criteria:

          -  Presence of major organ dysfunction (see above)

          -  Pregnancy

          -  Evidence of HIV infection or known HIV positive serology

          -  Patients or parents are psychologically incapable of undergoing BMT with associated
             strict isolation or documented history of medical non-compliance

          -  Patients >50 kg may be at risk for having cell doses below the goal of ≥ 10 x 106 CD
             34 cells/kg and therefore will not be eligible to receive unrelated PBSCs.