• Incidence of chronic graft-versus-host-disease (GVHD) [ Designated as safety issue: No ]
  
• Correlate cell populations with incidence of chronic GVHD [ Designated as safety issue: No ]
  
• Marrow inocula content of natural killer cells, dendritic cells, CD34, CD20, CD14, CD4, CD3, CD8, and naïve and memory T cells [ Designated as safety issue: No ]
  

• Engraftment and overall survival at 100 days and annually thereafter [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Minimize the incidence of chronic graft-versus-host disease (GVHD) by restricting the transplanted marrow dose in patients with severe aplastic anemia undergoing HLA-matched related bone marrow transplantation.
• Develop a better understanding of which cell subpopulations in the graft might contribute to chronic GVHD.
• Determine the content of natural killer cells, dendritic cells, CD34, CD20, CD14, CD4, CD3, CD8, and naïve and memory T cells in the marrow inocula.

Secondary

• Assess engraftment and overall survival of these patients.

OUTLINE: This is a multicenter study.

Patients receive cyclophosphamide IV over 1-2 hours on days -5 to -2 and antithymocyte globulin IV over 4-10 hours on days -4 to -2. Patients undergo an allogeneic reduced-dose bone marrow transplantation on day 0. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or orally twice daily on days -1 to 50, followed by a taper.

After completion of study treatment, patients are followed for 100 days and then annually thereafter.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of aplastic anemia with marrow failure, meeting 2 of the following criteria:

  • Granulocyte count < 500/mm³
  • Corrected reticulocyte count < 1%
  • Platelet count < 20,000/mm³

• No severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure, including any of the following:

  • Clonal cytogenetic abnormalities or myelodysplastic syndromes (preleukemia)
  • Fanconi's anemia
  • Aplasia secondary to radiotherapy or cytotoxic chemotherapy
  • Paroxysmal nocturnal hemoglobinuria that has not developed into aplastic anemia
• HLA-matched family member available as a donor

PATIENT CHARACTERISTICS:

• No severe organ toxicities, including any of the following:

  • Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
  • Severe hypoxemia, pO2 < 70 mm Hg, with decreased DLCO < 70% of predicted OR mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted
  • Impaired renal function, defined as creatinine > 2 times upper limit of normal OR creatinine clearance < 60 mL/min
• No fungal infections with radiological progression after receipt of amphotericin B or active triazole for > 1 month
• No HIV positivity
• Not pregnant or nursing
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No concurrent amphotericin B, antibodies, other investigational medications, or other blood products