Umbilical Cord Blood (UCB) Transplantation in Pediatric Patients With High Risk Leukemia and Myelodysplasia

The preparative regimen will consist of:

- Fludarabine: 25 mg/m2/day IV x 5 doses on Days -13, to -9

- Busulfan 1mg/kg IV every 6 hrs x 16 doses on Days -8 to -5

- Melphalan 45 mg/m2/day IV x 3 doses on days -4 to -2

- ATGAM 30mg/kg/day x 3 doses on Days -3 to -1

- Day 0 will be the day of the UCB Transplant

- The graft-versus-host-disease (GVHD) prophylaxis will be Cyclosporin A to maintain
level 200-400 beginning on Day -3, through 200-400. Solumedrol at 1mg/kg/day on Day 1
until D+4, then solumedrol 2mg/kg/day until Day +19 or till absolute neutrophil count
(ANC) reaches 500/mm2, then taper by 0.2 mg/kg/week.

Inclusion Criteria:

- Patients must be up to 21 years of age

- Patients cannot receive total body irradiation (TBI) because of:

- Young age - < 2 years at diagnosis of leukemia resulting in an age < 4 years at
transplantation (due to risk of severe growth retardation and brain damage).

- Inability to tolerate TBI because of prior radiation or organ toxicity.

- Refractory/multiply relapsed leukemia, for which a traditional
TBI/cyclophosphamide regimen would unlikely lead to a successful outcome.

- Patients must have a partially human leukocyte antigen (HLA)-matched UCB unit. Unit
must be HLA-matched minimally at 4 of 6 HLA-A and B (at intermediate resolution by
molecular typing) and DRB1 (at high resolution by molecular typing) loci with the
patient. The unit must deliver a pre-cryopreserved nucleated cell dose of at least
2.5 x 10^7 per kilogram.

- Acute myelogenous leukemia (AML) at the following stages:

- High risk first complete remission (CR1), defined as:

- Having preceding myelodysplasia (MDS)

- High risk cytogenetics (High-risk cytogenetics: del (5q) -5, -7, abn (3q),
t (6;9) complex karyotype (>= 5 abnormalities)

- Requiring > 2 cycles chemotherapy to obtain CR;

- Second or greater CR.

- First relapse with < 25% blasts in bone marrow.

- Patients with therapy-related AML whose prior malignancy has been in remission for at
least 12 months.

- Acute lymphocytic leukemia (ALL) at the following stages:

- High risk first remission, defined as:

1. Ph+ ALL; or,

2. Myeloid/lymphoid leukemia (MLL) rearrangement with slow early response [defined
as having M2 (5-25% blasts) or M3 (>25% blasts on bone marrow examination on Day
14 of induction therapy)]; or,

3. Hypodiploidy (< 44 chromosomes or DNA index < 0.81); or,

4. End of induction M3 bone marrow; or,

5. End of induction M2 with M2-3 at Day 42.

- High risk second remission, defined as:

1. Bone marrow relapse < 36 months from induction; or,

2. T-lineage relapse at any time; or,

3. Very early isolated central nervous system (CNS) relapse (6 months from
diagnosis); or,

4. Slow reinduction (M2-3 at Day 28) after relapse at any time.

- Any third or subsequent CR.

- Biphenotypic or undifferentiated leukemia in any CR or if in 1st relapse must have <
25% blasts in bone marrow (BM).

- MDS at any stage.

- Chronic myelogenous leukemia (CML) in chronic or accelerated phase.

- All patients with evidence of CNS leukemia must be treated and be in CNS CR to be
eligible for study.

- Patients ≥ 16 years old must have a Karnofsky score ≥ 70% and patients < 16 years old
must have a Lansky score ≥ 70%.

- Signed informed consent.

- Patients with adequate physical function as measured by:

1. Cardiac: Left ventricular ejection fraction at rest must be > 40%, or shortening
fraction > 26%

2. Hepatic: Bilirubin ≤ 2.5 mg/dL; and alanine transaminase (ALT), aspartate
transaminase (AST) and Alkaline Phosphatase ≤ 5 x upper limit of normal (ULN)

3. Renal: Serum creatinine within normal range for age, or if serum creatinine
outside normal range for age, then renal function (creatinine clearance or GFR)
> 70 mL/min/1.73 m2.

4. Pulmonary: Diffusing capacity of the lungs for carbon monoxide (DLCO), Forced
expiratory volume in 1 second (FEV1), Forced vital capacity (FVC) (diffusion
capacity) > 50% of predicted (corrected for hemoglobin); if unable to perform
pulmonary function tests, then O2 saturation > 92% of room air.

Exclusion Criteria:

- Pregnant (B-positive HCG) or breastfeeding.

- Evidence of HIV infection or HIV positive serology.

- Current uncontrolled bacterial, viral or fungal infection (currently taking
medication and progression of clinical symptoms).

- Autologous transplant < 6 months prior to enrollment.

- Prior autologous transplant for the disease for which the UCB transplant will be
performed.

- Allogeneic hematopoietic stem cell transplant < 6 months prior to enrollment.

- Active malignancy other than the one for which the UCB transplant is being performed
within 12 months of enrollment

- Active CNS leukemia.

- Requirement of supplemental oxygen.

- HLA-matched related donor able to donate.