• Toxicity [ Designated as safety issue: Yes ]
  
• Engraftment [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the lowest dose of total-body irradiation combined with cyclophosphamide and antithymocyte globulin that will achieve sustained engraftment in patients with severe aplastic anemia undergoing related or unrelated umbilical cord blood transplantation.

OUTLINE: This is a prospective, dose-finding study of total-body irradiation (TBI).

• Myeloablative conditioning regimen: Patients receive cyclophosphamide IV on days -7 to -4, -6 to -3, or -5 to -2 and anti-thymocyte globulin IV on days -6 to -4, -5 to -3, or -4 to -2.
• TBI: Patients undergo TBI twice daily on days -3, -2, and/or -1. Cohorts of 6 patients receive escalating or de-escalating doses of TBI until the optimal dose is determined. The optimal dose is defined as the dose at which ≤ 2 of 6 or 3 of 12 patients experience dose-limiting toxicity and ≤ 1 of 6 or 1 of 12 patients fail to engraft.
• Umbilical cord blood transplantation (UCBT): Patients undergo UCBT on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover.
• Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV or orally (twice daily for patients ≥ 6 years of age or 3 times daily for patients < 6 years of age) on days -1 to 180 and mycophenolate mofetil IV or orally (twice daily for patients ≥ 50 kg or 3 times daily for patients < 50 kg) beginning 4 hours after UCBT and continuing until approximately day 30.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of life-threatening marrow failure (severe aplastic anemia) of nonmalignant etiology meeting 2 of the following criteria:

  • Granulocyte count < 500/mm³
  • Corrected reticulocyte count < 1%
  • Platelet count < 20,000/mm³
• Failed to respond to the best available immunosuppressive treatment protocol by 75 days after initiation of therapy
• No paroxysmal nocturnal hemoglobinuria or Fanconi's anemia
• No clonal cytogenetic abnormalities or myelodysplastic syndromes
• No HLA-identical family member or closely matched (9 or 10 of 10 HLA-locus match) unrelated marrow donor available

• Umbilical cord blood (UCB) donor available

  • Unrelated UCB donor matched for ≥ 4 of 6 loci or related UCB donor matched for ≥ 3 of 6 loci at the HLA-A and -B antigen level and DRB1 allele level

  • If multiple units are selected, the following criteria apply:

    • The UCB units must be matched to each other for ≥ 4 of 6 loci
    • Each unit must contain ≥ 1.5 x 10^7 total nucleated cells (TNC) per kg recipient weight

PATIENT CHARACTERISTICS:

• No active fungal infections
• HIV negative
• No severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No concurrent aspirin or nonsteroidal anti-inflammatory drugs