Umbilical Cord Transplantation for the Elderly Population

Allogeneic stem cell transplantation is a life saving procedure in selected high-risk or
recurrent hematologic malignancies and marrow failure syndromes. However its wide application
is limited by availability of suitably HLA matched adult donors. Umbilical Cord Blood (UCB)
has been increasingly used as an alternative hematopoietic stem cell source for these
patients. To date, over 10,000 UCB transplants have been performed in both children32-38 and
adults.35,39-44 Its advantages include easier procurement, decreased risk to donors, reduced
risk of transmitting infections, the immediate availability of cryopreserved units, and
acceptable HLA mismatches. The transplantation of UCB allows a greater degree of HLA
mismatching without an unacceptably high incidence of graft versus host disease (GVHD). Adult
patients receiving myeloablative cord blood transplants have a 90% chance of engraftment, but
carry a 50% rate of transplant related mortality.

Inclusion Criteria:

- Ages 55-73

- Patients will have one of the following malignancies:

- Acute myelogenous leukemia (AML) deNovo in first CR with adverse cytogenetic
abnormalities, M0, M6, M7 subtypes, extramedullary disease in remission or high
CD34+ disease (> 50%)

- AML in early relapse (5-10% blasts on bone marrow aspirate or biopsy), or beyond
CR-1 with no circulating blasts

- AML at any time if resulting from a previous myelodysplasia

- Acute lymphocytic leukemia or lymphoblastic lymphoma (ALL) in first CR with
adverse prognostic features: t (9; 22), extra medullary disease, or mature B cell
phenotype

- Acute lymphoid leukemia or lymphoblastic lymphoma in early relapse (5- 10% blasts
on aspirate), or beyond CR-1

- Acute Undifferentiated Leukemia or biphenotypic leukemia in CR1 or CR2

- Transfusion dependent myelodysplastic syndrome (MDS) or refractory anemia with
excess blasts (RAEB) or RAEB-in transition, CMMOL, or any myelodysplasia with
7q-, 5q-, 7-, 5- or resulting from prior anti cancer therapy.

- Relapsed Non-Hodgkin's Lymphoma (NHL), including those that have relapsed after
an autologous marrow/blood stem cell transplant

- Chronic lymphocytic leukemia (CLL) patient who has had fludarabine and either
failed or relapsed. Prior autologous transplant patients are eligible.

- Patients with adequate organ function and performance status criteria

- Subject must have at least one or the following back-up stem cell sources in case of
engraftment failure:

- Subject is willing to undergo BM harvest or peripheral blood progenitor cells
(PBPC) collection for use in case of engraftment failure (when clinically
applicable).

- Subject has a second CBU as a possible back up.

- Subject's haploidentical family member has been identified and agreed (by signing
a written informed consent) to donate hematopoietic stem cells in case of
engraftment failure.

- Evaluation by social service/psychologist

- Subject signs the written informed consent after being aware of the nature of the
subject's disease and willingly consents to the treatment program after being informed
of alternative treatments, potential risks, benefits and discomforts.

- Ability to understand and agree to compliance with strict evaluation, isolation,and
medication schedules

- Designated primary care giver.

- Dental evaluation/treatment completed.

- ENT evaluation/treatment completed.

- All patient who survive to day 90 are eligible for measurement of T and B cell
function and lymphocyte subset numbers to determine immune reconstitution post UCB
transplantation with or without StemEx®

Exclusion Criteria:

- Patient with suitable related donor as defined per institutional guidelines

- Chemotherapy resistant or active AML, ALL, AUL, biphenotypic leukemia

- AML evolved from myelofibrosis

- MDS with 20% or greater bone marrow blasts at pre-transplant workup. Patients may
receive therapy and if in remission, are eligible

- Prior allogeneic hematopoeitic stem cell transplant at any time

- Less than twenty-one days have elapsed since the subject's last radiation or
chemotherapy prior to conditioning (except for hydroxyurea)

- Uncontrolled bacterial, fungal or viral infection at the time of study enrollment

- Seropositive or NAT positive for HIV, HTLV-1 and Hepatitis C

- Subjects with signs and symptoms of active central nervous system (CNS) disease

- Females who are pregnant or breastfeeding

- Allergy to bovine proteins or to aminoglycoside antibiotics (e.g. gentamicin) or to
any product, which may interfere with the treatment.

- Patient unable to give informed consent or unable to comply with the treatment
protocol including appropriate supportive care, follow-up and research tests.

- Enrolled in another clinical trial or received an investigational treatment during the
last 30 days, unless approved by the primary investigator.