The purpose of this research study is to evaluate the safety and efficacy of cell depletion in a donor lymphocyte infusion (DLI) product with the use of the CliniMACS machine. Previously, patients with hematologic malignancies who have relapsed after transplant have been given infusions of donor white blood cells calsed donor lymphocyte infusion (DLI) as a way to boost their immune function and fight cancer. Information from other research studies suggests that lowering the number of a certain type of white blood cell called CD25+ Tregs in the DLI may allow for a greater effect. In this research study, we are looking for the appropriate dose of DLI depleted of the CD25+ Treg white blood cells that can be given safely.

• The original marrow/stem cell donor will undergo one or two white blood cell collection procedures called leukopheresis. The cells collected from the first leukopheresis will be sent to the laboratory where the amount of white blood cells collected will be measured. If the number of cells collected at the first leukopheresis is not enough, the donor will have a second leukopheresis procedure.
• Once enough lymphocytes are collected from the donor, the CliniMACS CD25 Reagent System device will reduce the number of CD25+ Tregs. The CD25+ depleted donor lymphocytes will then be infused to the participant intravenously. Participants will be observed for about one hour after the infusion.
• One, two, four and eight weeks after the DLI, participants will return to the clinic for follow-up visits. At each visit a physical exam, questions about the participants general health, and blood tests will be performed.

Inclusion Criteria:

• Patients with hematologic malignancies that have relapsed after HLA-A, -B, -C, and-DRBI matched allogeneic hematopoietic stem cell transplantation
• At least 2 months following hematopoietic stem cell transplantation
• Off any systemic immunosuppressive medication for treatment or prevention of GVHD, for a minimum of 2 weeks prior to study entry
• Recipient with donor chimerism of 20% or greater within 6 weeks prior to DLI
• Patient with less than 50% bone marrow involvement (% cellularity) and less than 5cm lymph nodes, in the 6 weeks prior to DLI
• 18 years of age or older
• ECOG Performance Status score 0-2
• Prior stem cell donor is medically fit to undergo leukapheresis procedure

Exclusion Criteria:

• Relapsed CML in chronic phase
• Prior donor lymphocyte infusion or other immunotherapy treatment within 8 weeks prior to enrollment
• Chemotherapy within 4 weeks prior to enrollment
• Clinically significant and active autoimmune disease in donor or patient. This is defined as autoimmune disease resulting in organ dysfunction and/or requiring systemic therapy
• Evidence of active acute or chronic GVHD
• Uncontrolled infection