Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

OBJECTIVES:

Primary

- Determine the engraftment potential of umbilical cord blood (UCB) in patients with
hematological cancers.

- Determine the safety of UCB transplantation in these patients.

Secondary

- Determine the rate of neutrophil and platelet recovery and the completeness of donor
cell engraftment.

- Determine the incidence and severity of acute and chronic graft-versus-host disease.

- Determine the incidence of relapse in patients with malignant disease.

- Determine the probabilities of survival and event-free survival (EFS) at 1 and 2 years
after UCB transplantation.

OUTLINE: Patients are stratified according to degree of HLA disparity (0-1 vs 2-3 disparities
between donor and recipient), donor type (related vs unrelated), and the basis of cell dose
(< 2 vs ≥ 2 x 10^7 nucleated cells/kg recipient body weight). Patients are assigned to 1 of 4
treatment groups according to disease*.

NOTE: *Patients with acute lymphocytic leukemia (ALL), secondary acute myeloid leukemia
(AML), severe combined immunodeficiency, familial erythrophagocytic lymphohistiocytosis
(FEL)/viral-associated hemophagocytic syndrome (VAHS), inborn errors of metabolism, aplastic
anemia, Fanconi's anemia, or Diamond-Blackfan anemia who have an unrelated umbilical cord
blood donor may proceed directly to transplantation.

- Preparative regimen:

- Group 1 (patients with chronic myelogenous leukemia, AML, myelodysplastic
syndromes, or ALL): Patients receive cyclophosphamide IV once daily on days -7 and
-6. Patients then undergo total-body irradiation (TBI) twice daily on days -4 to
-1. Patients undergoing unrelated allogeneic umbilical cord blood transplantation
(UCBT) also receive methylprednisone IV and anti-thymocyte globulin (ATG) IV twice
daily on days -2 and -1.

- Group 2 (patients with infant leukemia): Patients receive busulfan orally or IV
four times daily on days -9 to -6 and melphalan IV once daily on days -4 to -2.
Patients undergoing unrelated allogeneic UCBT also receive methylprednisolone IV
and ATG IV twice daily on days -2 and -1.

- Group 3 (patients with inborn errors of metabolism): Patients receive busulfan
orally or IV four times daily on days -9 to -6 and cyclophosphamide IV once daily
on days -5 to -2. Patients undergoing unrelated allogeneic UCBT also receive
methylprednisolone IV and ATG IV twice daily on days -2 and -1.

- Group 4 (patients with aplastic anemia): Patients receive cyclophosphamide IV once
daily on days -6 to -3 and ATG IV twice daily on days -5 and -3. Patients then
undergo TBI once on day -2.

- Allogeneic UCBT: Patients undergo UCBT on day 0. Patients with inborn errors of
metabolism receive methylprednisolone IV before and after UCBT on day 0.

- Graft-versus-host disease (GVHD) prophylaxis: Patients receive 1 of the following
regimens:

- Related donor UCBT: Patients receive cyclosporine IV over 2 hours or orally
beginning on day -3 and continuing until day 60.

- Unrelated donor UCBT and myeloablative preparative regimen: Patients receive
cyclosporine orally or IV over 2 hours twice daily beginning on day -3 and
continuing until day 180. Patients also receive methylprednisolone IV twice daily
on days 5-19.

- Unrelated donor UCBT and nonmyeloablative preparative regimen: Patients receive
cyclosporine IV over 2 hours or orally twice daily beginning on day -3 and
continuing until day 180. Patients also receive mycophenolate mofetil IV or orally
beginning on day 5 and continuing until day 30 or 7 days after active GVHD is
controlled.

All patients receive filgrastim (G-CSF) IV beginning on day 1 and continuing until blood
counts recover.

Patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- Leukemia including, but not limited to, the following subtypes:

- Chronic myelogenous leukemia

- Acute myeloid leukemia (primary or secondary)

- Acute lymphoblastic leukemia

- Lymphoma

- Myelodysplastic syndrome

- Aplastic anemia

- Fanconi's anemia

- Diamond-Blackfan anemia

- Inborn errors of metabolism (e.g., Hurler syndrome, Maroteaux-Lamy syndrome,
myelodysplastic syndrome VI, metachromatic leukodystrophy, adrenoleukodystrophy,
and globoid cell leukodystrophy)

- Immune deficiency disorders

- Patients must meet the eligibility requirements outlined in currently active treatment
protocols of the University of Minnesota Bone Marrow Transplant Program

- HLA-identical or 1, 2, or 3 antigen mismatched umbilical cord blood (UCB) donor with
at least one DRB1 match available

- Unrelated or related donor

- UCB specimen must contain ≥ 2.0 x 10^7 nucleated cells/kg patient body weight

PATIENT CHARACTERISTICS:

- See Disease Characteristics

- No active infection

- No history of HIV infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- Not specified