Donor Umbilical Cord Blood Transplantation in Treating Patients With Leukemia, Lymphoma, or Nonmalignant Hematologic Disorders

• Status: Completed
• Trial end date: 2005-09-01
• Target enrollment: 0
• Participant gender: All

Summary

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

PURPOSE: Phase II trial to study the effectiveness of allogeneic umbilical cord blood transplantation in treating patients who have leukemia, lymphoma, or nonmalignant hematologic disorders.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Roswell Park Cancer Institute
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Antilymphocyte Serum; Busulfan; Cyclophosphamide; Cyclosporine; Cyclosporins; Fludarabine; Fludarabine phosphate; Melphalan; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

• Acute myeloid leukemia (AML)*

• With or without history of myelodysplastic syndromes (MDS)

• Patients in first complete remission (CR) (no greater than 5% blasts in marrow) with translocations t(8;21) and inv(16) are allowed provided they failed first-line induction therapy

• Patients in first CR (no greater than 5% blasts in marrow) with translocations t(15;17) are allowed provided at least 1 of the following is true:

• Failed first-line induction therapy

• Molecular evidence of persistent disease

• No patients in first CR and with Down syndrome

• Acute lymphoblastic leukemia (ALL)*, meeting 1 of the following criteria:

• Not in first CR (no greater than 5% blasts in marrow)

• In first CR and high risk as defined by 1 of the following:

• Hypoploidy (no more than 44 chromosomes)

• Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14) (excluding B-ALL) or +MLL gene rearrangement

• One of the following elevated WBC levels:

• WBC greater than 100,000/mm^3 if 6 to 12 months of age

• WBC greater than 200,000/mm^3 if between 10 and 17 years of age

• WBC greater than 20,000/mm^3 if 18 years of age and over (adult [over 18 years of age] patient stratum closed to accrual)

• Failed to achieve CR after 4 weeks of induction therapy

• B-ALL that is not in first CR or that meets at least 1 of the high-risk criteria specified above

• No translocation t(8;14)

• No blasts with surface immunoglobulins

• CD10 negative

• Undifferentiated leukemia*

• Infant leukemia*

• Biphenotypic leukemia*

• Chronic myelogenous leukemia, meeting 1 of the following criteria:

• Accelerated phase

• Chronic phase

• At least 1 year from diagnosis without an identified matched unrelated bone marrow donor AND unresponsive to or unable to tolerate interferon

• Blast crisis* (greater than 30% promyelocytes plus blasts in the marrow)

• One of the following MDS:

• Refractory anemia

• Refractory anemia with ringed sideroblasts

• Refractory anemia with excess blasts (RAEB)

• RAEB in transformation

• Chronic myelomonocytic leukemia

• Paroxysmal nocturnal hemoglobinuria

• Hodgkin's or non-Hodgkin's lymphoma beyond first CR or failed primary induction therapy

• Tumor displays chemosensitivity (greater than 50% reduction in mass size after the most recent therapy) NOTE: *Patients in third or greater medullary relapse or refractory disease (other than primary induction failures) or blast crisis receive the study busulfan/melphalan conditioning regimen)

OR

• Diagnosis of one of the following nonmalignant diseases :

• Acquired severe aplastic anemia (stratum closed to accrual)

• Unresponsive to medical therapy with anti-thymocyte globulin and/or cyclosporine

• Inborn errors of metabolism, including, but not limited to the following:

• Hurler's syndrome

• Adrenoleukodystrophy

• Maroteaux-Lamy syndrome

• Globoid cell leukodystrophy

• Metachromatic leukodystrophy

• Fucosidosis

• Mannosidosis

• Fanconi anemia documented by increased chromosomal fragility assays and meeting 1 of the following criteria (stratum closed to accrual):

• Severe pancytopenia

• Absolute neutrophil count less than 500/mm^3

• Platelet count less than 20,000/mm^3

• Hemoglobin less than 8 g/dL

• Morphologic evidence of MDS with clonal chromosomal abnormalities

• Leukemia transformation

• Other marrow failure syndromes, including any of the following (stratum closed to accrual):

• Blackfan-Diamond syndrome that is unresponsive to medical therapy

• Kostmann's congenital agranulocytosis unresponsive to medical therapy

• Congenital amegakaryocytic thrombocytopenia

• Thrombocytopenia absent radius

• Combined immune deficiencies including, but not limited to the following:

• Severe combined immunodeficiency (SCID)

• 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

• Nezeloff's syndrome

• Cartilage hair hypoplasia

• Reticular dysgenesis

• No active CNS leukemia (cerebrospinal fluid with WBC greater than 5/mm^3 and malignant cells on cytospin)

• No SCID patients who do not require cytoreduction

• No dyskeratosis congenita

• No primary myelofibrosis

• No grade 3 or greater myelofibrosis

• Familial erythrophagocytic lymphohistiocytosis patients must not have any of the following:

• Abnormal brain MRI

• Neurologic symptoms

• Lymphocytes and monocytes greater than 7/mm^3 in the cerebrospinal fluid

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

PATIENT CHARACTERISTICS:

Age

• 55 and under (over 18 closed to accrual)

Performance status

• Karnofsky 70-100% OR

• Lansky 50-100% (patients under 16 years old)

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• SGOT less than 5 times upper limit of normal

• Bilirubin less than 2.5 mg/dL

Renal

• Creatinine normal for age OR

• Creatinine clearance or glomerular filtration rate greater than 50% of lower limit of normal

Cardiovascular

• LVEF greater than 40% at rest and must improve with exercise* OR

• Shortening fraction greater than 26%* NOTE: *If symptomatic

Pulmonary

• DLCO greater than 45% of predicted* (corrected for hemoglobin)

• FEV_1 and FEC greater than 45% of predicted (corrected for hemoglobin) OR

• Room air oxygen saturation greater than 85%* NOTE: *If symptomatic

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No uncontrolled viral, bacterial, or fungal infection

• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

• More than 12 months since prior allogeneic stem cell transplantation with cytoreductive preparative therapy

• More than 6 months since prior autologous stem cell transplantation

Chemotherapy

• See Biologic therapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior enrollment on this study

• No continuous life support (e.g., mechanical ventilation) within 1 year after study transplantation (for patients with inborn errors of metabolism)