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

• Toxicity
• Engraftment

RATIONALE: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects and best dose of total-body irradiation when given together with cyclophosphamide and antithymocyte globulin in treating patients with severe aplastic anemia undergoing umbilical cord blood transplant.

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.

• Biological: anti-thymocyte globulin
• Biological: filgrastim
• Drug: cyclophosphamide
• Drug: cyclosporine
• Drug: mycophenolate mofetil
• Procedure: umbilical cord blood transplantation
• Radiation: total-body irradiation

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