OBJECTIVES: I. Determine the safety of total body irradiation and fludarabine followed by
allogeneic peripheral blood stem cell or bone marrow transplantation in combination with
cyclosporine and mycophenolate mofetil for establishing mixed chimerism in patients with
II. Determine whether this regimen can establish mixed chimerism in these patients.
III. Determine whether mixed chimerism is sufficient to reverse disease symptoms in these
IV. Determine the safety of donor lymphocyte infusions to eliminate persistent disease in
these patients with mixed chimerism.
PROTOCOL OUTLINE: Patients receive fludarabine IV over 2 hours on days -4 to -2 followed by
total body irradiation and peripheral blood stem cell or bone marrow transplantation on day
0. Patients also receive oral or IV cyclosporine 2-3 times daily on days -3 to 50 (related
donor) or 100 (unrelated donor) and oral mycophenolate mofetil twice daily on days 0 to 28
(related donor) or 40 (unrelated donor).
Patients may also receive donor lymphocyte infusion for continued treatment of symptoms in
the event of mixed chimerism and in the absence of graft-versus-host disease.
Patients are followed weekly for 1 month, monthly for 2 years, and then annually thereafter.
PROTOCOL ENTRY CRITERIA:
- Inherited disorders treatable with allogeneic peripheral blood or bone marrow
transplantation At high risk for regimen related toxicity with a conventional
- No severe CNS involvement of disease, defined by IQ score less than 70
- HLA matched donor Sibling donors must be a confirmed match at HLA-A, B, and DRB1
Other related and non-related donors must be matched at HLA-A, B, C, DRB1, and DQB1 A
donor homozygous for one allele only at HLA-A, B, C, DRB1, or DQB1 allowed (1 antigen
mismatch for graft-versus-host disease, 0 antigen mismatch for graft-rejection)
- No concurrent growth factors with mycophenolate mofetil
- Age: Under 55
- Performance status: Not specified
- Life expectancy: At least 100 days
- Hematopoietic: Not specified
- Hepatic: No evidence of synthetic dysfunction No severe cirrhosis
- Renal: Not specified
- Cardiovascular: LVEF at least 30% No poorly controlled hypertension on multiple
- Other: No organ dysfunction that would preclude survival Not pregnant or nursing
Fertile patients must use effective contraception during and for 12 months following