Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using One Haploidentical Donor

PRIMARY OBJECTIVES:

1) To assess 1 year relapse free survival in high risk patients undergoing hematopoietic stem
cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach with 2
days inserted between the last fraction of total-body irradiation (TBI) and the infusion of
donor T cells (donor lymphocyte infusion [DLI]).

SECONDARY OBJECTIVES:

1. To assess regimen related toxicity in this updated conditioning regimen,
graft-versus-host disease (GVHD) incidence and severity, and overall survival in
patients undergoing treatment on this protocol.

2. To assess the consistency and pace of engraftment.

3. To assess the pace of T cell and B cell immune recovery.

OUTLINE:

CONDITIONING REGIMEN: Patients undergo TBI twice daily (BID) on days -10 to -8, undergo DLI
on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -3 and -2.

TRANSPLANT: Patients undergo cluster of differentiation (CD) 34+ selected allogeneic HSCT on
day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV or orally (PO) beginning on day -1 with
taper beginning by day 42, and mycophenolate mofetil IV BID on days -1 to 28.

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

Inclusion Criteria:

1. This treatment is for patients with high risk hematologic malignancies. High risk is
defined as:

- Any patient with a hematologic malignancy with residual disease after treatment
with 1 or more chemotherapy regimens in whom achievement of remission with
additional chemoradiotherapy is felt to be unlikely

- Patients without morphologic evidence of disease but with high risk features
which would predict for relapse despite remission at HSCT such as adverse
cytogenetics, 3rd or greater CR (complete response), or failure to recover
peripheral blood counts to normal ranges. While these patients do not have
detectable disease by current methods, like all patients they have non-detectable
disease which in their case is highly aggressive.

2. Patients must have one related donor who is HLA (human leukocyte antigen) mismatched
in the GVHD direction at two or more HLA loci

3. Patients must adequate organ function:

- LVEF (left ventricular ejection fraction) of >50 %

- Diffusing capacity of the lungs for carbon monoxide (DLCO) (adjusted for
hemoglobin) >50 % of predicted and forced expiration to the full FEV-1 >50 %

- Adequate liver function as defined by a serum bilirubin <1.8, AST (aspartate
aminotransferase) or ALT (alanine aminotransferase) < 2.5X upper limit of normal

- Creatinine clearance of > 60 ml/min

4. Karnofsky Performance Status (KPS) of > 80% on the modified (KPS) tool

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

6. Able to give informed consent

Exclusion Criteria:

1. Modified (KPS) Karnofsky Performance status of <80%

2. > 5 Comorbidity Points on the Hematopoietic cell transplantation - specific
comorbidity (HCT-CI) Index (See Appendix B)

3. Class I or II antibodies against donor human leukocyte antigens (HLA)

4. HIV positive

5. Active involvement of the central nervous system with malignancy

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

7. Pregnancy, or unwillingness to use contraception if they have child bearing potential

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

9. Alemtuzumab treatment within 8 weeks of HSCT admission

10. Anti-thymocyte globulin (ATG) level of > 2 ugm/ml

11. Patients with active inflammatory processes including T max >101 or active tissue
inflammation are excluded

12. Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses
specified in the treatment plan