OBJECTIVES: I. Ascertain whether stem cell transplantation (SCT) is an effective method by
which missing or dysfunctional enzymes can be replaced in patients with various inborn
errors of metabolism.
II. Determine whether clinical manifestations of the specific disease may be arrested or
reversed by this treatment.
PROTOCOL OUTLINE: Patients receive either cyclophosphamide and high dose total body
irradiation (TBI) or busulfan and cyclophosphamide.
Cyclophosphamide IV is given on days -5 and -4 and TBI on days -2, -1, and 0. Busulfan is
given orally every 6 hours on days -9 through -6 and cyclophosphamide IV on days -5 through
-2. Patients rest on day -1.
Patients receive bone marrow infusion on day 0. For GVHD prophylaxis, patients receive
methotrexate on day 1, then on days 3, 6, and 11. Cyclosporine IV begins on day -2 over 12
hours, followed by continuous infusion for 21 days. Then, oral doses of cyclosporine are
given every 12 hours to patients who tolerate oral feeding. Cyclosporine is continued 6
months posttransplant, then tapered 10% per week and stopped.
Patients who receive genotypically HLA nonidentical stem cells undergo additional GVHD
prophylaxis with methylprednisolone (IV or PO) or its equivalent every 12 hours on days 3 to
day 100. Dose is then tapered as tolerated over 1 month.
Patients who receive cord blood stem cells receive methylprednisolone instead of
methotrexate for GHVD prophylaxis. Methylprednisolone is given 3 times daily beginning on
day 5 and continuing until day 17. Then, methylprednisolone is tapered 10% per week as
To accelerate engraftment, patients receive filgrastim IM daily beginning on day +1 and
continuing until ANC equals 5000.
PROTOCOL ENTRY CRITERIA:
- Hereditary enzymopathies, such as: Metachromatic leukodystrophy
- Congenital Immunodeficiencies
- Heritable hematologic disorders, such as: Thalassemia major Refractory
Diamond-Blackfan anemia Fanconi anemia Amegakaryocytic thrombocytopenia
- Age: Under 18
- Other: SCT is performed using a histocompatible related donor, an unrelated donor, or
an unrelated cord blood donor Haploidentical donors are accepted for patients with
severe congenital immunodeficiency