Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma

The study of whether an infusion of blood cells called lymphocytes from a donor can stimulate the immune system to fight your leukemia/lymphoma.

There have been important advances in the modulation of the immune system for the treatment of hematologic malignancies and solid tumors.

This protocol will build upon these previous observations as follows:

* Haploidentical peripheral blood pheresed cells will be used at 1-2x108 CD3 cells/kg.
* Total body radiation will not be utilized.

  * This modification may more effectively activate the recipient's immune system to attack their hematological malignancy by not damaging the recipient's immune cells prior to cellular infusion. Safety should be improved since the risk of graft versus host disease should be greatly reduced as the host's immune system will not be conditioned.
* Granulocyte-colony stimulating factor (G-CSF) priming will not be used.

  * In our first clinical trial, G-CSF priming was not used for matched transplants. Our second trial did employ G-CSF priming in the haplo-identical setting. Previous data has cited a role for G-CSF in stimulation of invariant Natural Killer(NK) cells with enhanced GVL effects11. However, our most recent laboratory data with unprimed PBMC has shown effective cell kill activity without the addition of G-CSF. As G-CSF would be administered to healthy volunteers, the unclear benefit of the addition of this cytokine is offset by the potential side effects such as headache, fever, and bone pain. G-CSF mobilization serves to shift the response from a TH1 to TH2 through the increased production of T regulatory cells. The end result would be a decrease in immune stimulation. Since the goal of this study is to NOT have engraftment, the manipulation of the donor cells to dampen the host versus tumor stimulation is not needed nor desired. Furthermore, since this protocol is not a stem cell transplant, stem cells do not need to be mobilized with G-CSF.

It is important to note that the proposed study is not a stem cell transplant study. In the situation of stem cell transplants, the goal of the procedure is to have engraftment, or sustainable donor chimerism in the marrow to provide hematopoietic reconstitution as well as immunologic reconstitution. In this study, we are evaluating the use of donor lymphocytes (not stem cells) to stimulate an immune response of the recipients' immune system.

Eligibility Criteria:
Inclusion Criteria:

* Histologic confirmation of hematological malignancy consisting of the following leukemias/lymphomas:
* Mantle cell lymphoma with Ki-67\>30%
* Diffuse Large Cell Lymphoma
* Burkitts Lymphoma
* Systemic T Cell Lymphomas
* Acute Myeloid Leukemia
* Acute Lymphoblastic Leukemia
* Recurrence or progression of hematological malignancy after at least 1 prior standard treatment with progression within 6 months from last treatment.
* No curative treatment option is available.

  -\> 4-weeks since prior chemotherapy or radiation to cellular therapy infusion. (Hydroxyurea may be utilized up to 48 hours prior to initiation of treatment on this protocol).
* Age equal to or greater than 18 years.
* Patients with a history of invasive second malignancy unless disease free for \> 5 years.
* Patients must have an expected life expectancy of at least 2 months at the time of initiation of treatment.
* No active systemic infection.
* Patients who have relapsed after standard autologous stem cell infusion are eligible as long as they meet all inclusion criteria and no exclusion criteria. These patients must be out more than 6 months from cell infusion to be eligible for enrollment.
* DLCO \> 40% with no symptomatic pulmonary disease.
* LVEF \> 40% by MUGA or echocardiogram.
* Creatinine \< 2.0 mg/dl. Total bilirubin less than 1.5x the upper limit of normal (ULN), AST \< 3x ULN.
* Non-pregnant and willing to use appropriate birth control during the duration of the study period.

Exclusion Criteria:

* Evidence of HIV infection.
* Any uncontrolled severe, concurrent illness which in the opinion of the treating physician would make this protocol treatment unreasonably hazardous for the patient.
* Oxygen dependent obstructive pulmonary disease.
* Failure to demonstrate adequate compliance with medical therapy and follow-up.
* Significant medical or psychiatric illness that would impair the ability to participate in protocol therapy.
* For women of reproductive potential, refusal to use effective form of contraception.
* Previous allogeneic stem cell transplant
* Patients who have had previous purine analog (fludarabine, pentostatin, 2-CDA) -Patients with chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma, and indolent lymphoma (follicular lymphoma, marginal zone lymphoma)
* Patients with HLA antibodies to donor HLA type.