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

Fecha de inicio: 1 de diciembre de 1998

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