Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases

This is a study to collect routine clinical data from UCBT using unrelated single or double
UCB units as an alternative, non-HLA-matched stem cell source for patients with hematological
diseases.

- data collection from transplant preparative therapy consisting of treatments with
chemotherapeutic regimens and total body irradiation.

- data collection from umbilical cord blood selection and infusion.

- data collection from standard supportive disease and transplant related care.

Pre- and post-transplant medication, UCB selection and infusion, supportive care, and
follow-up will be according to the current University of Minnesota BMT guidelines.

An average of 18 patients are expected to be treated on this protocol per year.

Inclusion Criteria:

- Eligible Disease Status

- Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high
risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic
leukemia; CR2+. All patients must be in CR as defined by hematological recovery,
AND <5% blasts by light microscopy within the bone marrow with a cellularity of
≥15%.

- Very high risk pediatric patients with AML: Patients <21 years, however, are
eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or
more cycles of chemotherapy.

- Acute Lymphocytic Leukemia (ALL): high risk CR1 as defined by cytogenetics (such
as t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1
abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal
residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR
as defined by hematological recovery, AND <5% blasts by light microscopy within
the bone marrow with a cellularity of ≥15%.

- Very high risk pediatric patients with ALL: patients <21 years are also
considered high risk CR1 if they had M2 or M3 marrow at day 42 from the
initiation of induction or M3 marrow at the end of induction. They are eligible
once they achieved a complete remission.

- Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in
first chronic phase (CP1) patient must have failed or be intolerant to imatinib
mesylate.

- Plasma Cell Leukemia after initial therapy, who achieved at least a partial
remission

- Advanced Myelofibrosis

- Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory
Anemia with severe pancytopenia or high risk cytogenetics: Blasts must be < 10%
by a representative bone marrow aspirate morphology.

- Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone
B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease
progression/relapse within 12 of achieving a partial or complete remission.
Patients who had remissions lasting > 12 months, are eligible after at least two
prior therapies. Patients with bulky disease (nodal mass greater than 5 cm)
should be considered for de-bulking chemotherapy before transplant.

- Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are
eligible after initial therapy in CR1+ or PR1+.

- Large Cell NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6
months) are eligible.

- Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after
initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1
year.

- Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first
response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be
considered for this protocol after initial therapy.

- Myeloproliferative Syndromes

- Availability of suitable UCB unit(s)

- 0 to 55 years

- Voluntary written consent (adult or parental/guardian)

Exclusion Criteria:

- previous irradiation that precludes the safe administration of TBI - Radiation
Oncology will evaluate all patients who have had previous radiation therapy

- chemotherapy refractory large cell and high grade NHL (ie progressive disease after >
2 salvage regimens)

- if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18
years old prior myeloablative allotransplant or autologous transplant

- extensive prior therapy including > 12 months alkylator therapy or > 6 months
alkylator therapy with extensive radiation

- pregnant or breastfeeding

- HIV positive