Reduced Intensity Haploidentical Transplant for Hematological Malignancies

Haploidentical hematopoietic stem cell transplant is a life saving therapy for patients who
are without well matched donors. This type of therapy has been associated with poor outcomes
in the past due to complications such as infection. The Jefferson 2 Step approach was
designed to allow the infusion of an exact dose of tolerized lymphocytes in haploidentical
transplant in order to allow for immune reconstitution post transplant to avoid infectious
complications while still having acceptable rates of GVHD. In this approach, older patients
or patients who were transplanted previously with high-risk hematological malignancies
undergo chemotherapy with fludarabine and cytarabine or thiotepa. The patients then receive
an exact dose of their donors' lymphocytes. The phase I portion of the study determined the
optimal dose of lymphocytes. Two days after receiving the donor lymphocytes, the patients
receive 2 daily doses of cyclophosphamide. The purpose of the cyclophosphamide is for in-vivo
tolerization of the lymphocytes. One day after receiving cyclophosphamide, the patients
receive stem cell from their donor. Tacrolimus and mycophenolate mofetil are used as GVHD
prophylaxis.

Inclusion Criteria:

1. Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is
thought to be beneficial, and in whom front-line therapy has already been applied.

2. Patients must have a related donor who is a two or more allele mismatch at the
HLA-A;B; C; DR loci.

3. Patients who have sibling donors with a one antigen mismatch due to recombination will
not be enrolled in this protocol.

4. Patients must adequate organ function:

1. LVEF of >45%

2. DLCO >45% of predicted corrected for hemoglobin

3. Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X
upper limit of normal

4. Serum creatinine < 2.0 mg/dl or creatinine clearance of > 40 ml/min

5. Performance status > 70% (Karnofsky)

6. Patients must be willing to use contraception if they have childbearing potential

7. Able to give informed consent

Exclusion Criteria:

1. Performance status of < 70% (Karnofsky)

2. HIV positive

3. Active involvement of the central nervous system with malignancy

4. Psychiatric disorder that would preclude patients from signing an informed consent

5. Pregnancy

6. Patients with life expectancy of < 6 months for reasons other than their underlying
hematologic/oncologic disorder or complications there from.

7. Patients who have received alemtuzumab within 8 weeks of transplant admission, or who
have recently received horse or rabbit anti-thymocyte globulin and have ATG levels of
> 2 µgm/ml.

8. Patients who cannot receive cyclophosphamide

9. Patients with evidence of another malignancy, exclusive of a skin cancer that requires
only local treatment, should not be enrolled on this protocol