Reduced Intensity Chemotherapy and Radiation Therapy Before Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

PRIMARY OBJECTIVES:

I. To demonstrate efficacy of this approach over the historical 2 step reduced intensity
conditioning (RIC) approaches in the "vulnerable" population defined as: patients with
hematopoietic cell transplant (HCT)-co-morbidity index (CI)/age scores >= 2, but no more than
a score of 5 as based on the Sorror et al. data.

SECONDARY OBJECTIVES:

I. To compare the non-relapse mortality (NRM) and relapse related mortality (RRM) rates at 1
year for patients treated on this study to the that of patients undergoing haploidentical RIC
hematopoietic stem cell transplantation (HSCT) as reported in the literature and as observed
in the 2 step RIC trials.

II. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients
undergoing treated on the Thomas Jefferson University (TJU) RIC 2 step approach.

III. To evaluate engraftment rates and lymphoid reconstitution in patients treated on the TJU
RIC 2 step approach.

OUTLINE:

RIC: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -10 to
-8 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients also undergo total body
irradiation (TBI) followed by a donor lymphocyte infusion (DLI) on day -6.

TRANSPLANT: Patients undergo cluster of differentiation (CD)34+ peripheral blood stem cell
transplant on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus orally (PO) beginning day -1 with a taper
initiated on day 42 and mycophenolate mofetil IV twice daily (BID) on days -1 to 28 in the
absence of GVHD.

After completion of study treatment, patients are followed up for 1 year.

Inclusion Criteria:

1. Patients treated on this study will have:

1. Acute myeloid leukemia in morphologic CR not requiring treatment for their
disease for 6 weeks

2. A history of AML with < 20% residual blasts after induction therapy and
persisting with <20% blasts for at least 8 weeks without reinduction.

3. RA or RARS or isolated 5q- can proceed to transplant without any treatment

4. RAEB-1, RCMD+/-RS, or MDS NOS with stable disease for 6 months (as documented by
serial bone marrow examinations) in the absence of any therapy but growth factors
or transfusion support. Patients who require treatment to "control their disease"
must show chemo-responsiveness

5. CMML or RAEB-2 must demonstrate chemo-responsiveness. Chemo-responsiveness is
defined as a blast percentage decrease by at least 5 percentage points and there
must be less than 20% blasts after treatment and at the time of transplant

6. Hodgkin or Indolent Non-Hodgkin's lymphoma

7. Myeloma with < 5% plasma cells in the marrow

8. Myeloproliferative disorders

9. Aplastic Anemia

10. A hematological or oncological disease (not listed) in which allogeneic HSCT is
thought to be beneficial, and the disease is chemoresponsive.

11. Patients without clear manifestation of their disease status in terms of stage
and/or responsiveness should be discussed with the PI and enrollment analysis
should be documented in the study records.

2. Patients must have a related donor who is HLA mismatched at 2, 3, or 4 antigens at the
HLA-A; B; C; DR loci in the GVHD direction. (Patients with related donors who are HLA
identical or are a 1-antigen mismatch may be treated on this therapeutic approach, but
will have their outcomes will not be part of the statistical aims of the study (see
Statistical Section). The HLA matched related category includes patients with a
syngeneic donor.

3. Patients must have had front line therapy for their disease.

4. Patients must adequate organ function:

1. LVEF (Left ventricular end diastolic function) of >45%. LVEF between 45% and 54%
must have negative stress test with increase in EF of 3-5 points with stress

2. DLCO (Diffusing Capacity of the Lung for Carbon Monoxide ) ≥45% of predicted
corrected for hemoglobin, FEV-1 (forced expiratory volume at 1 second ≥50% of
predicted

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

4. Creatinine Clearance of ≥ 60 mL/min

5. HCT-CI/Age Score ≤ 5 points (Patients with greater than 5 points will be allowed for
trial with approval of the PI and the Co-PI or his designee. This is an adjustment to
account for healthy patients who meet the spirit of this protocol but have histories
that result in higher than HCT-CI 5 points. An example is a patient with a solid tumor
malignancy in their remote history (adds 3 points to HCT-CI total) where the treatment
for the malignancy occurred years to decades before and there has been complete
recovery of toxicities.

6. KPS≥ 90% patients older than 70 years, KPS≥ 80% patients younger than 70 years

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

Exclusion Criteria:

1. Performance status < 90% in patients 70 years old or greater, <80% in patients less
than age 70 years

2. HCT-CI/age Score >5 points (Patients with greater than 5 points will be allowed for
trial with approval of the Principal Investigator and the Co-Principal Investigator or
his designee. This is an adjustment to account for healthy patients who meet the
spirit of this protocol but have histories that result in higher than HCT-CI 5 points.
An example is a patient with a solid tumor malignancy in their remote history (adds 3
points to HCT-CI total) where the treatment for the malignancy occurred years to
decades before and there has been complete recovery of toxicities.

3. A diagnosis of CMML, unless in morphologic CR

4. HIV positive

5. Active involvement of the central nervous system with malignancy

6. Inability to obtain informed consent from patient or surrogate

7. Pregnancy

8. Patients with life expectancy of < 6 months for reasons other than their underlying
hematologic/oncologic disorder

9. Patients who have received alemtuzumab or antithymocyte globulin within 8 weeks of the
transplant admission. The absence of these therapies in the medical record will serve
as documentation that they were not given.

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