This clinical trial is studying how well giving cyclophosphamide together with anti-thymocyte globulin followed by methotrexate and cyclosporine works in preventing chronic graft-vs-host disease (GVHD) in patients with severe aplastic anemia undergoing donor bone marrow transplant. Giving low doses of chemotherapy, such as cyclophosphamide, before a donor bone marrow transplant helps stop the growth of abnormal cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving anti-thymocyte globulin before and methotrexate and cyclosporine after transplant may stop this from happening

PRIMARY OBJECTIVES:

I. Minimize the incidence of chronic GVHD by restricting the transplanted marrow dose to 2.0-2.5 x 10^8 nucleated cells/kg.

SECONDARY OBJECTIVES:

I. Engraftment and overall survival.

OUTLINE:

CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2.

TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0.

GVHD PROPHYLAXIS: Patients receive methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or orally (PO) twice daily on days -1 to 50, followed by a taper until 6 months after grafting.

After completion of study treatment, patients are followed up at on day 180, 1 year, 1.5 years, 2 years, 3 years, and yearly thereafter.

Inclusion Criteria:

• Any patient who has aplastic anemia with marrow failure involving 2 of the three following criteria: granulocytes < 500/uL; a corrected reticulocyte count of < 1%; platelet count of < 20,000/uL
• Availability of an human leukocyte antigen (HLA)-matched family member
• DONOR: Family member who is HLA-matched
• DONOR: If more than one HLA-matched family member is available, priority will be given to a donor who is genotypically HLA-identical, of appropriate cytomegalovirus (CMV) serology, ABO compatible, and, in case of a female donor, non-parous

Exclusion Criteria:

• Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure:

  • Patients who have developed clonal cytogenetic abnormalities or myelodysplastic syndrome (preleukemia)
  • Patients with Fanconi's anemia
  • Aplasia secondary to radiation or cytotoxic chemotherapy
  • Patients with paroxysmal nocturnal hemoglobinuria who have not developed aplastic anemia

• Severe organ toxicities:

  • Cardiac insufficiency requiring treatment or symptomatic coronary artery disease;
  • Severe hypoxemia , partial pressure of oxygen (pO2) < 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted;
  • Impaired renal function (creatinine > 2 times upper limit of normal or estimated creatinine clearance < 60 ml/min)

• Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month

• Human immunodeficiency virus (HIV)-positive patients

• Females who are pregnant or breast-feeding

• DONOR: Donors who have increase anesthetic risk and are not able psychologically and medically to tolerate the procedure

• DONOR: HIV-positive donors