This study is designed to determine whether Umbilical Cord Transplantation (UCB) can be
substituted for adult bone marrow cells in the standard stem cell transplant regimens used
at this hospital for subjects who do not have stem cell donors.
Allogeneic stem cell transplantation (SCT) following myeloablative and non-myeloablative
conditioning therapy has proven curative treatment for a number of inherited and acquired
hematologic disorders. The success of allogeneic transplantation is largely determined by
compatibility between donor and recipient, which predicts the risk of fatal
graft-versus-host disease (GVHD). Unfortunately, less than one third of patients needing an
allogeneic transplant have an available compatible donor in their family. Registries have
been established to match patients with compatible volunteer (unrelated) donors, but many
patients, and in particular minority patients, still lack stem cell donors.
Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells, which is readily
available from the placenta following childbirth. Blood banks have been established in the
United States and abroad to collect, process and store UCB for use in allogeneic
transplantation. To date, more than 2000 UCB transplants have been performed in adults and
children around the world.
Rationale for use of Umbilical Cord Blood in Transplantation
UCB has a number of proven and theoretical advantages as an alternative source of
hematopoietic stem cells for transplantation:
1. Placental or umbilical cord blood is an abundantly available source of stem cells,
which is currently discarded and can be harvested at no risk to the mother or infant.
2. Important infectious agents, particularly CMV, are much less common in the newborn than
adults, and are less likely to contaminate UCB collections.
3. UCB collections, typed, cryopreserved and banked, are available on demand, eliminating
delays and uncertainties that now complicate marrow collection from unrelated donors.
At present, UCB can be delivered for infusion within days of the initiation of a
search. This compares with a median of 3 months from search to delivery of stem cells
through the registries of volunteer adult donors.
4. The intensity of graft-versus-host reactivity of fetal lymphocytes appears to be less
than that of adult cells and consequently fetal lymphocytes are more tolerant of HLA
incompatibility. Published studies have shown that transplantation of UCB matched at
4-5/6 antigens results in a comparable incidence of GVHD to transplantation of
unrelated stem cells fully matched at 6/6 antigens.
5. Frozen UCB can be easily shipped, stored at the treating institution, and thawed for
use when needed, compared to freshly donated stem cells which have a limited shelf-life
of one day or less, necessitating coordination between harvesting surgeons,
transportation, and transplantation teams.
This research study has been designed for people who have been diagnosed with a blood tumor,
which has not responded to treatment or has recurred, a bone marrow failure state such as
aplastic anemia, or one of certain inherited metabolic disorders; and whose doctor feels the
best treatment is an allogeneic stem cell transplant (alloSCT) but a related or unrelated
adult donor is not available. Instead, a single unit of umbilical cord blood (UCB) will be
used as the source of the subject's immune system. This study is designed to determine
whether a single unit of UCB can be substituted for adult bone marrow cells in the standard
stem cell transplant regimens used at this hospital for subjects who do not have stem cell
Patients meeting eligibility criteria for unrelated allogeneic stem cell transplantation
may be considered for participation on this clinical trial if and only if they meet each
of the following criteria:
- Patients must have one of the following diagnoses
- Relapsed or refractory hematologic malignancy, or
- High risk hematologic malignancy in first remission, or
- Refractory acquired marrow failure state, or
- Inherited disorder of metabolism or marrow failure state without alternative curative
- Patients must not have a 6/6 or 5/6 HLA-matched related donor.
- Patients must not have a HLA-A, -B and -DRB1 high resolution matched unrelated donor
following registry search, or cannot (in the opinion of the treating physician) wait
the median 3 months to receive a MUD unit.
- Patients must demonstrate an ability to understand and willingness to sign the
informed consent document
Patients considered for myeloablative conditioning must satisfy the following additional
- Patients must be up to age 55 (inclusive)
- Patients must have serum direct bilirubin ≤ 2.0 mg/dl and transaminases ≤ 2x
institution upper limit of normal
- Patients must have serum creatinine ≤ 2 mg/dl with creatinine clearance ≥ 60 ml/min
(either calculated or measured).
- Patients must have MUGA scan or echocardiogram normal for the institution, but not
less than 45% left ventricular ejection fraction and no clinical evidence of cardiac
- Patients must have an ECOG performance status of 0 or 1 (see Appendix C).
- Patients must have adequate pulmonary function when corrected for hemoglobin and
alveolar volume as evidenced by a diffusion capacity and FEV1 > 50% of predicted.
Patients considered for reduced-intensity conditioning must satisfy the following
- Patients must not be candidates for myeloablative conditioning due to any one of the
following: Prior myeloablative stem cell transplantation, Age > 50, Co morbid illness
- In opinion of treating physician, unable to comply with or withstand rigors of
- Patients with leukemia must have circulating and bone marrow blast counts < 5%, all
other patients must have chemotherapy responsive disease
- Patients must be between the ages of 18 and 70 (inclusive)
- Patients must have serum direct bilirubin ≤ 2.0 mg/dL and transaminases ≤ 3x
institution upper limit of normal
- Patients must have creatinine clearance ≥ 30 ml/min (either calculated or measured).
- Patients must have MUGA scan or echocardiogram documenting left ventricular ejection
fraction of no less than 35% and no clinical evidence of cardiac dysfunction.
Patients must have an ECOG performance status of 0 or 1 (see Appendix C).
Patients must have adequate pulmonary function when corrected for hemoglobin and alveolar
volume as evidenced by a diffusion capacity and FEV1 ≥ 40% of predicted.
Patients are ineligible for participation on this trial if they meet any of the following
- Patients with a history of myocardial infarction within the preceding 6 months,
significant arrhythmia within the preceding 3 months, uncontrolled hypertension or
congestive heart failure are ineligible.
- Patients with unstable angina are not eligible.
- Pregnant or lactating women are ineligible.
- Male and female patients who do not agree to practice approved methods of birth
control for the duration of the study are ineligible.
- Patients with uncontrolled infection are ineligible.
- Patients who are HIV positive or have evidence of chronic viral hepatitis are
- Patients unable to comply with requirements for compliance with therapeutic plan
and/or scheduled evaluations