Double Cord Blood Transplant for Patients With Malignant and Non-malignant Disorders

Allogeneic stem cell transplantation from an human leukocyte antigen (HLA) matched related
family donor is the treatment of choice for a wide variety of malignant and non-malignant
disorders. Unfortunately, only 25% of potential recipients have an HLA matched related family
donor, leaving approximately 75% of potential recipients requiring alternative sources of HLA
matched allogeneic stem cells. One potential source of HLA matched allogeneic stem cells is
from unrelated adult donors that have been identified in the national and international donor
registries. However, several limitations restrict the uniform utilization of unrelated
allogeneic adult donors including ethnic background of the recipient, acuity and timing of
planned allogeneic transplant, availability of donor, and high risk of severe acute
graft-versus-host disease (GVHD) (III/IV), among others. The investigators have recently
identified a new alternative source of allogeneic stem cells, unrelated cryopreserved
placental/cord blood stem cells.

Inclusion Criteria:

- Patients will be eligible for double cord blood stem cell transplant (TNC ≥ 4x107/kg
of two combined units) if available single cord blood has TNC ≤4.0 x 107/kg and they
lack a matched (5-6/6) family donor, a 10/10 unrelated adult donor, and/or if their
disease status required emergent stem cell transplant and they could not wait 2-3
months for searching for a matched unrelated adult donor.

- Adequate renal function defined as:Serum creatinine <1.5 x normal, or Creatinine
clearance or radioisotope glomerular filtration rate (GFR) >60 ml/min/m2 or >60
ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range.

- Adequate liver function defined as:Total bilirubin <1.5 x normal, or serum
glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum
glutamic pyruvic transaminase (SGPT) (alanine aminotransferase (ALT)) <3.0 x normal

- Adequate cardiac function defined as:Shortening fraction >27% by echocardiogram, or
Ejection fraction >47% by radionucleotide angiogram or echocardiogram.

- Adequate pulmonary function defined as:Uncorrected diffusing capacity of the lungs for
carbon monoxide (DLCO) 50% by pulmonary function test.For children who are
uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse
oximetry >94% on room air.

Eligibility for Moderate Intensity, Reduced Intensity Regimen and Fanconi's Anemia
(Regimens C, D and E)

- Adequate renal function defined as: Serum creatinine <2.0 x normal, or Creatinine
clearance or radioisotope GFR 40 ml/min/m2 or >40 ml/min/1.73 m2 or an equivalent GFR
as determined by the institutional normal range.

- Adequate liver function defined as:Total bilirubin <2.5 x normal, or SGOT (AST) or
SGPT (ALT) <5.0 x normal

- Adequate cardiac function defined as:Shortening fraction of >25% by echocardiogram, or
Ejection fraction >40% by radionucleotide angiogram or echocardiogram.

- Adequate pulmonary function defined as:Uncorrected DLCO >35% by pulmonary function
test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise
intolerance, and a pulse oximetry >94% on room air.

Exclusion Criteria:

- Females who are pregnant or breast-feeding

- Patients with documented uncontrolled infection at the time of study entry