Unrelated Umbilical Cord Blood As An Alternate Source Of Stem Cells Transplantation

OBJECTIVES:

• Determine 180-day survival in patients with malignant or nonmalignant hematologic diseases treated with allogeneic umbilical cord blood transplantation. (Severe aplastic anemia, Fanconi anemia, and marrow failure syndromes strata are closed to accrual; adult [over 18 years of age] patient stratum is closed to accrual.)
• Determine disease-free and long-term survival in patients treated with this regimen.
• Determine the incidence of neutrophil engraftment, primary and secondary graft failure, platelet engraftment, and red blood cell engraftment in patients treated with this regimen.
• Determine the incidence and severity of acute and chronic graft-versus-host disease in patients treated with this regimen.
• Determine the incidence of complications, including infection, veno-occlusive disease, and interstitial pneumonitis, in patients treated with this regimen.
• Determine the incidence of relapse, other malignancies, lymphoproliferative disorders, and posttransplantation myelodysplasia in patients treated with this regimen.
• Determine the immune reconstitution in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are grouped according to the following strata:

• Stratum I: Malignant disease, 5/6 or 6/6 HLA match, age 18 and under

• Stratum II: Malignant disease, 4/6 HLA match, age 18 and under

• Stratum III: Malignant disease, 3/6 HLA match, age 18 and under

• Stratum IV: Malignant disease, 2/6 or 1/6 HLA match, age 18 and under

• Stratum V (closed to accrual): Severe aplastic anemia, Fanconi anemia, or other marrow failure syndrome

• Stratum VI: Inborn errors of metabolism/storage diseases and other nonmalignant diseases not included in stratum V

• Stratum VII: Malignant disease receiving alternative conditioning regimen comprising busulfan and melphalan

• Stratum VIII (closed to accrual): Adult patients (over age 18)

• Conditioning therapy: Patients are assigned to 1 of 5 groups according to diagnosis.

• Group I (malignant disease or severe aplastic anemia [severe aplastic anemia closed to accrual]): Patients undergo total body irradiation (TBI) once or twice daily on days -8 to -4. Patients then receive cyclophosphamide IV on days -3 and -2, methylprednisolone IV on days -3 to 0, and antithymocyte globulin (ATG) IV once or twice daily on days -3 to -1.

• Group II (Fanconi anemia [closed to accrual]): Patients undergo TBI on day -6, and then receive cyclophosphamide IV and fludarabine IV on days -5 to -2, and methylprednisolone IV and ATG IV on days -5 to -1.

• Group III (inborn errors of metabolism/storage disease): Patients receive oral busulfan 4 times daily on days -9 to -6, cyclophosphamide as in group II, and methylprednisolone and ATG as in group I.

• Group IV (other nonmalignant diseases): Patients receive conditioning therapy as in group III. Patients with familial erythrophagocytic lymphohistiocytosis or Langerhans cell histiocytosis also receive etoposide on days -5 to -3.

• Group V (non-TBI regimen for leukemia patients under 2 years of age): Patients receive oral busulfan 4 times daily on days -8 to -5, melphalan IV on days -4 to -2, and methylprednisolone and ATG as in group I.

• Allogeneic umbilical cord blood transplantation: All patients undergo umbilical cord blood transplantation on day 0. Beginning on day 0 or 1, patients receive filgrastim (G-CSF) IV or subcutaneously daily until blood counts recover.

• Graft-versus-host disease prophylaxis: Patients receive cyclosporine (IV or oral) beginning between days -3 and -1 and continuing for 1 year after transplantation and methylprednisolone twice daily beginning on day 1 and continuing until blood counts recover.