Stem Cell Transplantation for Hurler

Phase 2

Completed

Conditions: Mucopolysaccharidosis I
Mucolipidosis Type II (I-cell Disease)
Mannosidosis
Mucopolysaccharidosis VI

Interventions: Procedure: Stem Cell Transplant
Drug: Busulfan, Cyclophosphamide, ATG

Brief 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.

Detailed Description: Prior to transplantation, subjects will receive Busulfan intravenously (IV) via the Hickman line four times 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 subjects to help the new marrow "take" and grow.

On the day of transplantation, the donor's hematopoietic cells will be transfused via central venous catheter.

After hematopoietic cell transplant, subjects will then receive two drugs, cyclosporin and either methylprednisolone or Mycophenolate Mofetil (MMF). Cyclosporin and methylprednisolone or MMF are given to help prevent the complication of graft-versus-host disease and to decrease the chance that the new donor cells will be rejected.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Busulfan, Cyclophosphamide, ATG	All patients treated with chemotherapy and transplantation.
Treatment Arm	Stem Cell Transplant	All patients treated with chemotherapy and transplantation.

Primary Outcome Measures

Name	Time	Method
Mean Percentage of Donor Cells in Study Population (Chimerism).	at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year	Donor-derived engraftment determined by restriction fragment length polymorphism (RFLP).

Secondary Outcome Measures

Name	Time	Method
Number of Patients Surviving on Study	at 100 days, 1 year, and 3 years post transplant	Number of patients surviving (alive) at specified timepoints.
Number of Patients Who Failed Engraftment.	Day 42 Post Transplant	Toxicity (undesireable effect) of hematologic donor cell engraftment is determined by failure to engraft at Day 42.
Number of Patients With Grade III-IV Acute Graft-versus-host Disease (aGVHD).	Day 100 Post Transplant	Toxicity (undesireable effect) of this stem cell transplant preparative regimen due to acute graft-versus-host disease.