Palifermin With Leuprolide Acetate for the Promotion of Immune Recovery Following Total Body Irradiation Based T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation

Patients will be randomized to one of two arms: palifermin with Lupron, and control. The
control arm consists of a standard TCD allo-HSCT without the addition of palifermin or
Lupron.

Patients randomized to receive Lupron will receive a three month depot dose 3-6 weeks prior
to the start date of the pre-transplant conditioning regimen. Patients assigned to receive
palifermin will receive this drug at 60mcg/kg/day IV on three consecutive days, 24 hours
apart with the last dose administered no less than 24 and no more than 48 hours prior to the
start of cytoreduction. The preparative regimen to be used for transplants will consist of:
hyperfractionated TBI administered in 11 doses over 4 days for a total of 1375 cGy, thiotepa
5 mg/kg/day IV x 2 days and cyclophosphamide with mesna prophylaxis 60 mg/kg/day IV x 2 days.
All patients will receive ATG for two doses prior to transplant, except recipients of
mismatched grafts (in the GVHD vector) will receive three doses. G-CSF mobilized CD34 PBSCs
obtained from the HLA compatible donor will be infused on day 0. Patients assigned to receive
palifermin will receive three additional daily doses of the drug, the first approximately 6
hours after the stem cell infusion on day 0, followed by two daily doses given at 24 hour
intervals on d+1 and d+2. Patients assigned to receive Lupron will receive a further 3-month
depot injection approximately 3 months (+/- one week) post the first dose. Supportive care
will be administered as per the BMT Service guidelines. The conditioning regimen may be
modified to allow an extra day during conditioning or prior to the graft infusion if required
by donor and/or patient scheduling restrictions.

Inclusion Criteria:

Treatment Portion:

- AML in 1st remission - for patients whose AML does not have "good risk" cytogenetic
features (i.e. t (8;21), t(15;17), inv 16 without c-kit mutations).

- Acute leukemias of ambiguous lineage in ≥ 1st remission

- Secondary AML in remission

- AML in ≥ 2nd remission

- ALL in 1st remission with clinical or molecular features indicating a high risk for
relapse; or ALL ≥ 2nd remission

- CML failing to respond to or not tolerating imatinib, dasatinib or nilotinib in first
chronic phase of disease; CML in accelerated phase, second chronic phase, or in CR
after accelerated phase or blast crisis.

- Non-Hodgkins lymphoma with chemo responsive disease in any of the following
categories:

intermediate or high grade lymphomas who have failed to achieve a first CR or have relapsed
following a 1st remission who are not candidates for autologous transplants.

b.ii. any NHL in remission which is considered not curable with chemotherapy alone and not
eligible/appropriate for autologous transplant.

- Myelodysplastic syndrome (MDS): RA/RCMD with high risk cytogenetic features or
transfusion dependence, RAEB-1 and RAEB-2

- Chronic myelomonocytic leukemia: CMML-1 and CMML-2.

- Patient's age is ≥18 or ≤60 years old

- Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status ≥ 70%

- Patients must have adequate organ function measured by:

Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve
with exercise.

- Pulmonary: asymptomatic or if symptomatic, DLCO > 60% of predicted (corrected for
hemoglobin)

- Hepatic: < 3xULN ALT and < 1.5 total serum bilirubin, unless there is congenital
benign hyperbilirubinemia

- Renal: serum creatinine < 1.2 mg/dL or if serum creatinine is outside the normal
range, the CrCl > 50 ml/min (measured or calculated/estimated)

- Patients have a plan to receive a CD34-selected peripheral blood stem cell transplant
with TBI-based conditioning.

Exclusion Criteria:

- Active extramedullary disease

- Active and uncontrolled infection at time of transplantation

- Patients who have undergone a prior allogeneic or autologous stem cell transplant
within the previous six months.

- Pregnant or breast feeding

- HIV infection

- Patient is felt to not be a candidate for TBI by the BMT service

Donor Inclusion Criteria:

- Donor must be willing and able to undergo PBSC collection.