2-Step Approach to Stem Cell Transplant in Treating Participants With Hematological Malignancies

PRIMARY OBJECTIVES:

I. To assess whether providing a patient with "5+5" dosing in a 2 step matched related donor
hematopoietic stem cell transplantation (HSCT) increases the percentage of patients who
achieve full donor chimerism earlier as defined by 98% or greater donor T cell chimerism at
28 days post HSCT (d+28).

SECONDARY OBJECTIVES:

I. To assess day (d) +90 chimerism in patients receiving "5+5" dosing. II. To assess post
HSCT relapse rates in patients receiving "5+5" dosing. III. To assess rates of grade II-IV
graft versus host disease (GVHD) in patients receiving "5+5" dosing.

IV. To assess treatment-related mortality (TRM) in patients receiving "5+5" dosing.

Inclusion Criteria:

- Provide signed and dated informed consent form.

- Have a hematological malignancy or any type of dyscrasia in which allogeneic HSCT is
thought to be beneficial.

- Have a related donor who is no more than a 1-antigen mismatch at the human leukocyte
antigen (HLA)-A; B; C; DR loci in the GVHD direction with the patient. (Patients with
a syngeneic donor may be treated on this therapeutic approach, but their outcomes will
not be part of the statistical aims of the study.

- LVEF (left ventricular end diastolic function) of >= 45%.

- DLCO (diffusing capacity of the lung for carbon monoxide) >= 50% of predicted
corrected for hemoglobin.

- FEV-1 (forced expiratory volume at 1 second >= 50% of predicted.

- Serum bilirubin =< 1.8.

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper
limit of normal.

- Creatinine clearance of >= 60 mL/min.

- Have a Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) score =< 5 points
(patients with greater than 5 points will be allowed for trial with approval of the
principal investigator [PI] and at least 1 co-investigator [co-I] not on the primary
care team of the patient). 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.

- Have a Karnofsky performance score (KPS) >= 80%.

- Women of reproductive potential (defined as women under the age of 50 years still
menstruating within 2 months of HSCT despite past history of chemotherapy) will be
counseled to use highly effective contraception including oral, intramuscular (IM), or
patch contraceptives, intrauterine device (IUD), diaphragm, cervical cap, or
contraceptive implant. Pharmacological avoidance of pregnancy and suppression of
menstruation may be instituted during the HSCT inpatient stay.

- Men will be asked to abstain from sexual relations during the treatment period of the
HSCT stay.

- DONOR: All donors are selected and screened for their ability to provide adequate
infection-free apheresis products for the patient in a manner that does not put the
donor at risk for negative consequences.

Exclusion Criteria:

- Be human immunodeficiency virus (HIV) positive.

- Be pregnant or breastfeeding.

- Have received alemtuzumab or rabbit antithymocyte globulin (ATG) within 8 weeks or
horse ATG within 6 weeks of the transplant admission. This exclusion criterion will be
documented by the absence of these drugs in the medical record.

- Patients with evidence of another malignancy, exclusive of a skin cancer that requires
only local treatment, should not be enrolled on this protocol without the specific
approval of the PI. If the PI disregards this criterion (example of this is localized
prostate cancer not yet requiring treatment), the rationale must be documented in the
study binder). This exclusion criterion will be documented by the absence of these
drugs in the medical record.