Umbilical Cord Blood for Stem Cell Transplantation in Treating Young Patients With Malignant or Nonmalignant Diseases

The Use Of Umbilical Cord Blood As A Source Of Hematopoietic Stem Cells

RATIONALE: Umbilical cord blood transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy.

PURPOSE: This phase II trial is studying how well umbilical cord blood works as a source of stem cells in treating patients with types of cancer as well as other diseases.

OBJECTIVES:

Primary

• Determine the impact of the use of umbilical cord blood as a source of hematopoietic stem cells for children with life-threatening oncologic, hematologic, or genetic/metabolic disorders in need of a stem cell transplant.
• Compare the incidence of graft-versus-host disease in patients receiving cord blood transplants in this study with historical data for unrelated donor stem cell transplants.
• Compare the incidence of engraftment in patients receiving cord blood transplants in this study with historical data for unrelated donor stem cell transplants.

OUTLINE:

• Preparative therapy: Patients are treated on 1 of 4 preparative therapy regimens.

  • Regimen A: Patients undergo total body irradiation (TBI) two times daily on days -7 to -4. Patients receive cyclophosphamide IV over 30-60 minutes on days -3 and -2 and anti-thymocyte globulin (ATG) IV over at least 6 hours on days -3 to -1.
  • Regimen B (patients who do not receive TBI): Patients receive oral busulfan 4 times daily on days -8 to -5, and ATG IV over at least 6 hours and melphalan IV over 15-20 minutes on days -4 to -2.
  • Regimen C (patients with Fanconi's anemia and related disorders): Patients undergo TBI on day -6. Patients receive ATG IV over at least 6 hours and methylprednisolone IV on days -5 to -1 and fludarabine IV over 30 minutes and cyclophosphamide IV over 30-60 minutes on days -5 to -2.
  • Regimen D: Patients receive oral or IV busulfan 4 times daily on days -9 to -5, ATG IV over at least 6 hours on days -5 to -3, and cyclophosphamide IV over 30-60 minutes on days -5 to -2.

• Cord blood transplant: All patients undergo umbilical cord blood transplantation on day 0.

• Graft-versus-host disease prophylaxis: Patients receive oral or IV cyclosporine twice daily beginning on day -1. Patients also receive methylprednisolone IV twice daily beginning on day 5 and continuing until at least day 28.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of malignant or non-malignant disease, including but not limited to any of the following:

  • Acute myeloid leukemia or acute lymphoblastic leukemia (ALL) with resistant disease beyond first clinical remission (CR)

  • ALL in first CR at high-risk because of 1 of the following factors:

    • Hypoploidy

    • Pseudodiploidy with translocations t(9;22), t(4;11), or t(8;14)

    • Elevated WBC at diagnosis as follows:

      • > 100,000/mm^3 for patients 6-12 months of age
      • > 50,000/mm^3 for patients 10-20 years of age
      • > 20,000/mm^3 for patients 21 years of age

    • Burkitt's lymphoma/leukemia

  • Chronic myelogenous leukemia in first chronic phase or beyond

  • Juvenile myelomonocytic leukemia

  • Advanced stage or relapsed lymphoma

  • Advanced stage or relapsed solid tumors, including any of the following:

    • Neuroblastoma
    • Ewing's sarcoma
    • Rhabdomyosarcoma

  • Myelodysplastic syndromes, excluding patients with grade 3 or 4 myelofibrosis

  • Familial erythrophagocytic histiocytosis

  • Histiocytosis unresponsive to medical management

  • Inborn errors of metabolism

  • Langerhans cell histiocytosis unresponsive to medical management

  • Immune deficiencies, including:

    • Severe combined immune deficiency
    • Wiskott-Aldrich

  • Hemoglobinopathies, including sickle cell disease and thalassemia

  • Severe aplastic anemia

  • Fanconi's anemia

  • Metabolic storage diseases

• Unrelated cord blood donor must be HLA-identical OR may be mismatched for 1, 2, or 3 HLA-loci (A, B, DR)

• No other existing HLA-identical related donor available at the time of transplantation

PATIENT CHARACTERISTICS:

Age

• 21 and under

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Not specified

Renal

• Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified