Umbilical Cord Blood Transplantation From Unrelated Donors

PRIMARY OBJECTIVES:

I. Determine the kinetics of engraftment of umbilical cord blood (UCB) following transplantation into unrelated individuals.

II. Determine the incidence of non-engraftment and secondary graft failure when unrelated donor UCB cells are administered to patients receiving myeloablative, reduced intensity cytoreductive, or non-ablative conditioning regimens together with immunosuppressive therapy.

III. Determine the incidence and severity of graft-vs-host disease (GVHD) for patients receiving unrelated donor UCB grafts.

IV. Document the overall survival, disease-free-survival, and rates of relapse for UCB transplant recipients.

OUTLINE: This is an observational study.

Patients undergo a conditioning regimen per standard of care at the discretion of the treating provider, followed by a planned UCB transplantation on study. Patients also have their medical records reviewed for engraftment data on study.

Inclusion criteria

• Appropriate diagnosis: Patients must have a disease or syndrome amenable to therapy with hematopoietic stem cell transplantation. Diagnoses include, but are not limited to:
• Congenital and Other Non-malignant Disorders:
• Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome)
• Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital Osteopetrosis, Osteogenesis Imperfecta)
• Metabolic disorders (e.g. Hurler's Syndrome)
• Severe aplastic anemia
• High-Risk Leukemia:
• Acute Myelogenous Leukemia
• Refractory to standard induction therapy (more than 1 cycle required to achieve remission)

• Recurrent (in CR ≥ 2)
• Treatment-related AML or MDS
• Evolved from myelodysplastic syndrome
• Presence of FLT3 abnormalities
• FAB M6 or M7
• Adverse cytogenetics
• Myelodysplastic Syndrome
• Acute Lymphoblastic Leukemia including T lymphoblastic leukemia:
• Refractory to standard induction therapy (time to CR >4 weeks)
• Recurrent (in CR ≥ 2)
• WBC count >30,000/mcL at diagnosis
• Age >30 at diagnosis
• Adverse cytogenetics, such as t(9:22), t(1:19), t(4:11), and other MLL rearrangements.
• Chronic Myelogenous Leukemia in accelerated phase or blast crisis
• Biphenotypic or undifferentiated leukemia
• Burkitt's leukemia or lymphoma
• Lymphoma:
• Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemo-sensitive, and ineligible for an autologous stem cell transplant or previously treated with autologous SCT
• Marginal zone or follicular lymphoma that is progressive after at least two prior therapies
• Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible for an autologous HSCT
• Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and disease status
• Adequate organ function:
• Cardiac - LVEF >45%, or shortening fraction >25%, Absence of congestive heart failure or conduction disturbances with high risk for sudden death
• Pulmonary - DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted;
• Renal - serum Cr < 1.5 times the upper limit of normal for age or GFR ≥ 50 ml/min/1.73m2
• Hepatic - total bilirubin level < 2 times the upper limit of normal (except for patients with Gilbert's syndrome or hemolysis); if the primary disease process is causal, this criterion will be reconsidered. ALT, AST, and Alkaline phosphatase ≤ 5 times upper limit of normal.
• Performance Status Karnofsky or Lansky score ≥ 70%.
• Informed Consent must be obtained prior to initiating conditioning therapy.
• Receipt of viable cord blood product(s), single or dual, must be confirmed with the stem cell processing laboratory prior to initiating conditioning therapy.

Exclusion criteria

• Availability of 10/10 or 9/10 HLA-matched related or unrelated donor within a reasonable timeframe dictated by the clinical urgency of the transplant
• Autologous HSCT < 6 months prior to proposed UCB transplant
• Pregnant or breast feeding
• Current uncontrolled infection
• Evidence of HIV infection or positive HIV serology