• Umbilical cord blood (UCB) engraftment (defined as UCB-derived absolute neutrophil count [ANC] ≥ 500 cells/μL) on day 42 [ Designated as safety issue: No ]
  

• CD34+ cell dose and CD3+ cell dose [ Designated as safety issue: No ]
  
• Degrees of UCB, haploidentical related donor CD34+ cell, and recipient chimerism in T-lymphocyte, NK cell, and myeloid lineages assessed by PCR of short tandem repeats (STRs) [ Designated as safety issue: No ]
  
• ANC recovery rate (ANC ≥ 500 cells/µL) on day 22 [ Designated as safety issue: Yes ]
  
• Days to an UCB-derived ANC of 500 cells/µL and 1,000 cells/µL [ Designated as safety issue: Yes ]
  
• Platelet recovery (days to a platelet count of 20,000/mm³ and 50,000/mm³ and days to transfusion independence) [ Designated as safety issue: Yes ]
  
• Red blood cell recovery (days to transfusion independence) [ Designated as safety issue: Yes ]
  
• Incidence and severity of acute graft-vs-host disease (GVHD) [ Designated as safety issue: No ]
  
• Incidence and severity of chronic GVHD [ Designated as safety issue: No ]
  
• Graft failure (loss of the graft ) as measured by chimerism [ Designated as safety issue: No ]
  
• Non-hematological effects attributable to the preparative regimen [ Designated as safety issue: No ]
  
• Disease progression or relapse [ Designated as safety issue: No ]
  
• Transplant-related mortality before and after day 100 and day 200 [ Designated as safety issue: Yes ]
  
• Disease free-survival and overall survival [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To evaluate the potential of > 80% of patients with severe aplastic anemia or myelodysplastic syndromes associated with severe neutropenia refractory to immunosuppressive therapy to achieve engraftment of the umbilical cord blood (UCB) unit (defined as UCB-derived absolute neutrophil count [ANC] ≥ 500 cells/μL) by day 42 when treated with a nonmyeloablative conditioning regimen comprising cyclophosphamide, fludarabine phosphate, anti-thymocyte globulin, and total-body irradiation followed by donor umbilical cord blood transplantation and haploidentical related donor CD34+ peripheral blood stem cell transplantation.

Secondary

• To evaluate ANC recovery rate (ANC ≥ 500 cells/μL) on day 22.
• To evaluate the safety of this novel transplant regimen (non-hematologic toxicities).
• To evaluate treatment-related mortality on day 100 and day 200.
• To determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD) following treatment with this transplant regimen.

OUTLINE:

• Nonmyeloablative preparative conditioning regimen: Patients receive cyclophosphamide IV over 60 minutes once daily on days -7 and -6, fludarabine phosphate IV over 30 minutes once daily on days -5 to -1, and anti-thymocyte globulin IV over 4 hours once daily on days -5 to -2. Patients also receive a single dose of total-body irradiation over 30 minutes on day -1.
• Donor stem cell transplantation: Patients undergo donor umbilical cord blood transplantation and haploidentical related donor CD34+ peripheral blood stem cell transplantation on day 0.
• Graft-versus-host-disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally twice daily beginning on day -4 and continuing for at least 6 months and mycophenolate mofetil IV or orally twice daily beginning on day 0 and continuing for 100 days. Patients also receive oral prednisone or methylprednisolone IV beginning on day -5 (prior to the first dose of ATG) and continuing until day 19.

After completion of study treatment, patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

DISEASE CHARACTERISTICS:

• Diagnosed of 1 of the following:

  • Severe aplastic anemia characterized by all of the following:

    • Bone marrow cellularity < 30% (excluding lymphocytes)
    • Transfusion dependence for platelets and/or RBCs
    • Neutropenia (absolute neutrophil count [ANC] < 500 cells/μL)
    • Failed at least two forms of immunosuppressive therapy

  • Myelodysplastic syndromes characterized by all of the following:

    • Refractory anemia (RA) OR RA with ringed sideroblasts (RARS)
    • Neutropenia (ANC < 500 cells/μL)
    • Refractory to one or more lines of therapy
    • History of 1 or more opportunistic infections related to neutropenia

• At least one HLA-haploidentical (≥ 3/6 HLA matched) related donor (2-75 years old) available

  • No HLA identical or 5/6 HLA-matched related stem cell donor available
  • At least 2 x 10^6 CD34+ cells/kg required from haploidentical related donor
  • No haploidentical related donor with sickling hemoglobinopathies, including HbSS, HbAS, or HbSC

• At least one 4/6 HLA-matched (HLA-A, B, and DR loci) umbilical cord blood (UCB) unit from the National Marrow Donor Program available

  • UCB unit must contain a minimum total nucleated cells (TNC) (prior to thawing) of ≥ 1.5 x 10^7 cells/kg of recipient body weight

    • UCB unit must contain ≥ 1.7 x 10^5 CD34+ cells/kg (prior to thawing) if the minimum criterion of TNC is not met
• Not deemed to be a candidate for a 6/6 HLA-matched related or unrelated stem cell transplantation

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Transaminases ≤ 5 times upper limit of normal
• Serum bilirubin ≤ 4 mg/dL
• Creatinine clearance ≥ 50 mL/min
• DLCO ≥ 40% predicted
• Left ventricular ejection fraction ≥ 40% by ECHO OR ≥ 30% by MUGA
• HIV-negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No major anticipated illness or organ failure incompatible with survival from transplant
• No severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant regimen unlikely and make informed consent impossible
• No active infection not adequately responding to appropriate therapy
• No history of a malignant disease that is liable to relapse or progress within 5 years

PRIOR CONCURRENT THERAPY:

• At least 45 days since prior immunosuppressive therapy with horse anti-thymocyte globulin (ATG) or rat-ATG