A Multicenter Study of Unrelated Umbilical Cord Blood as an Alternate Source of Stem Cells for Transplantation

Inclusion Criteria

DISEASE CHARACTERISTICS:

- One of the following diagnoses:

- Acute myeloid leukemia (AML), with or without myelodysplastic syndromes

- Not in first complete remission (CR)* with translocations t(8;21) and inv
(16) unless failure of first-line induction therapy

- Not in first CR* with translocations t(15;17) abnormality unless:

- Failure of first-line induction therapy OR

- Molecular evidence of persistent disease

- Not in first CR with Down syndrome

- Patients with third or greater medullary relapse or refractory disease
(other than primary induction failures) receive busulfan/melphalan
conditioning regimen NOTE: * CR defined by no greater than 5% blasts in
marrow

- Acute lymphocytic leukemia (ALL)

- Not in first CR OR

- High-risk ALL in first CR, with high risk defined as one of the following:

- Hypoploidy (no greater than 44 chromosomes)

- Pseudodiploidy with translocations or molecular evidence of t(9;22),
11q23, or t(8;14) (except B-cell ALL) with or without MLL gene
arrangement

- Elevated WBC at presentation

- Age 6-12 months: greater than 100,000/mm^3

- Age 10-17 years: greater than 200,000/mm^3

- Age 18: greater than 20,000/mm^3

- Failed to achieve CR after 4 weeks of induction therapy

- Patients with B-ALL must not be in first CR, must meet at least one of the
high-risk criteria specified above, or must not meet any of the following
criteria:

- Translocation t(8;14)

- Blasts have surface immunoglobulins

- CD10 positive

- Patients with third or greater medullary relapse or refractory disease
(other than primary induction failures) receive busulfan/melphalan
conditioning regimen

- Chronic myelogenous leukemia, meeting criteria for 1 of the following:

- Accelerated phase

- Chronic phase if 1 year from diagnosis without a matched unrelated bone
marrow donor AND unresponsive to or unable to tolerate interferon

- Blast crisis, defined as greater than 30% promyelocytes plus blasts in bone
marrow

- Patients receive busulfan/melphalan conditioning regimen

- Acute undifferentiated leukemia (AUL), infant leukemia, or biphenotypic leukemia

- Patients with third or greater medullary relapse or refractory disease
(other than primary induction failures) receive busulfan/melphalan
conditioning regimen

- Juvenile myelomonocytic leukemia meeting the following criteria:

- No Philadelphia chromosome

- Bone marrow blasts less than 30%

- Peripheral blood monocytes greater than 1,000/mm^3

- At least 2 of the following:

- Peripheral blood spontaneous growth and/or sargramostim (GM-CSF)
hypersensitivity

- Increased hemoglobin F for age

- Clonal abnormalities (e.g., monosomy 7 or RAS mutations)

- Peripheral blood with myeloid precursors

- WBC greater than 10,000/mm^3

- Myelodysplastic syndromes defined by the following:

- Refractory anemia (RA)

- RA with ringed sideroblasts

- RA with excess blasts (RAEB)

- RAEB in transformation

- Chronic myelomonocytic leukemia

- Paroxysmal nocturnal hemoglobinuria

- Hodgkin's lymphoma or non-Hodgkin's lymphoma beyond first CR or primary
induction failures AND chemosensitive (greater than 50% reduction in tumor mass
size)

- Inborn error of metabolism including, but not limited to, Hurler's syndrome,
adrenoleukodystrophy (ALD), Maroteaux-Lamy syndrome, globoid cell
leukodystrophy, metachromatic leukodystrophy, fucosidosis, or mannosidosis

- For ALD patients over age 5, IQ must be at least 80

- For all other patients over age 5, IQ must be at least 70

- For all patients age 5 and under, developmental quotient or clinical
neurodevelopmental examination should demonstrate potential for
stabilization at a level of functioning where continuous life support
(e.g., mechanical ventilation) would not be predicted to be required in the
year after transplantation

- Combined immune deficiencies including, but not limited to:

- Severe combined immunodeficiency (SCID) requiring cytoreduction

- Wiskott-Aldrich syndrome

- Leukocyte adhesion defect

- Chediak-Higashi disease

- X-linked lymphoproliferative disease

- Adenosine deaminase deficiency

- Purine nucleoside phosphorylase deficiency

- X-linked SCID

- Common variable immune deficiency

- Nezelof's syndrome

- Cartilage hair hypoplasia

- No dyskeratosis congenita

- No ALL, AML, AUL, or biphenotypic leukemia in third or higher medullary relapse or
refractory disease other than primary induction failure

- No primary myelofibrosis or myelofibrosis grade 3 or worse

- No active CNS leukemia involvement (CSF with WBC greater than 5/mm^3 and malignant
cells on cytospin)

- No consenting 5/6 or 6/6 HLA-matched related donor available

- 3-6/6 HLA-matched unrelated umbilical cord blood donor available

PATIENT CHARACTERISTICS:

Age:

- See Disease Characteristics

- 18 and under

Performance status:

- Karnofsky 70-100%, if age 16 to 18

- Lansky 50-100%, if under age 16

Life expectancy:

- Not specified

Hematopoietic:

- See Disease Characteristics

Hepatic:

- Bilirubin less than 2.5 mg/dL

- SGOT less than 5 times upper limit of normal

Renal:

- Creatinine normal for age OR

- Creatinine clearance or glomerular filtration rate greater than 50% lower limit of
normal for age

Cardiovascular:

- If symptomatic:

- LVEF greater than 40% (or shortening fraction greater than 26%) and improves
with exercise OR

- Shortening fraction greater than 26%

Pulmonary:

- If symptomatic:

- DLCO, FEV_1, and FEC greater than 45% predicted OR

- Oxygen saturation greater than 85% on room air

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No uncontrolled viral, bacterial, or fungal infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- See Disease Characteristics

- At least 1 year since prior allogeneic stem cell transplantation (SCT) with
cytoreductive preparative therapy

- At least 6 months since prior autologous SCT

- No concurrent thrombopoietic growth factors

Chemotherapy:

- See Disease Characteristics

- See Biologic therapy

Endocrine therapy:

- Not specified

Radiotherapy:

- Not specified

Surgery:

- Not specified