Cyclophosphamide and Anti-thymocyte Globulin Followed By Methotrexate and Cyclosporine in Preventing Chronic Graft-Versus-Host Disease in Patients With Severe Aplastic Anemia Undergoing Donor Bone Marrow Transplant

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