Umbilical Cord Blood Transplantation From Unrelated Donors

This study is a single-center treatment protocol with four possible preparative regimens,
designed to validate the process of umbilical cord blood stem cell transplantation at our
institution. Enrolled patients will receive chemotherapy +/-total body radiation as a
pre-transplant conditioning regimen. Patients will then receive cord blood stem cells
followed by GvHD prophylaxis that will include Tacrolimus and Mycophenolate Mofetil, or
Cyclosporin A and Methylprednisolone. Multiple data points will be collected prior to,
during, and following transplantation to ensure safety of the process and to evaluate the
stated objectives.

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