Inclusion Criteria

- INCLUSION CRITERIA:

Treatment Subjects:

- Patients must have received allotransplant (related or unrelated donor) for
hematologic malignancies and have disease progression with a component of solid-phase
disease. Eligible diagnoses will include any acute or chronic leukemia with a
solid-phase component, Hodgkin's lymphoma, any non-Hodgkin's lymphoma, including
mantle cell lymphoma, multiple myeloma. Pathology slides from patients' pretransplant
diagnoses will be reviewed by NCI/CCR Department of Pathology.

- Patients must have at least two distinct sites of disease:

- At least one site must be in solid phase and amenable to irradiation, determined by
Radiation Oncology evaluation.

- In addition to the target(s) of irradiation, there must be disease that is discrete
from local effects of the radiation that can be evaluated for systemic response to
therapy.

- Patients must have disease that has failed to respond after a minimum of four weeks
to:

- Evidence of complete donor-T cell engraftment (greater than 90% chimerism) of the
circulating T cells

- A trial of tapering immunosuppressive therapy, including trials that are discontinued
due to development or flare of GVHD

- Patients must be 18 - 75 years of age.

- ECOG ECOG less than or equal to 3 (Karnofsky greater than or equal to 50%).

- Life expectancy greater than or equal to 1 month.

Arm A

- Patients with minimal to no clinical evidence of acute GVHD (Grade 0-I) or mild-
chronic GVHD (GVHD Score of no more than 1 in no more than two organ systems) while
off of systemic immunosuppressive therapy.

- Available source of clinical donor lymphocyte cell product, including stem
cell-mobilized product.

- Patients whose related allotransplant donor is available, eligible and enrolled on
this or another NIH/CC protocol that permits collection of a clinical donor
lymphocyte cell product, and donors are first-degree relatives with genotypic
identity at 5-6/6 HLA loci (HLA- A, B, and DR. Haploidentical (less than 5/6
genotypic identity) allotransplant recipients will not be eligible, due to risk of
severe GVHD with DLI.

- Patients whose related or unrelated allotransplant donors are unavailable or
ineligible, but who have cryopreserved donor lymphocyte cell products available for
use on this trial.

Arm B

- Patients with history of GVHD. Specifically:

- Patients who have a past history of resolved grade III acute GVHD or
moderate/severe chronic GVHD and who are no longer requiring systemic therapy to
treat GVHD.

- Patients who require continued prophylaxis with steroid-sparing agents, e.g.,
cyclosporine. Due to concerns that sirolimus (rapamycin) could interfere with
the potential efficacy of radiation-enhanced allogeneic cell therapy, patients
on sirolimus as part of GVHD control must be switched to another agent two weeks
prior to enrollment.

- Patients with GVHD controlled with local therapy, e.g., topical steroids,
budesonide.

- Patients with controlled acute GVHD (Grade I-III) or chronic-moderate/severe
GVHD on a stable (at least four weeks) or tapering dose of systemic
immunosuppression will be eligible for enrollment.

- Patients who do not have donor lymphocytes available for use on this trial, including
recipients of unrelated donor allografts.

- Patients whose allotransplant was from a haploidentical (less than 5/6 genotypic
identity) related donor.

- Provision for a Durable Power of Attorney.

- Ability to give informed consent.

Donor Subjects:

- Donors are the same individual whose cells were used as the source for the enrolling
Arm A Treatment Subject or DLI Control Subject's original allotransplant.

- Age 18 - 90.

- Adequate venous access for peripheral apheresis, or consent to use a temporary
central venous catheter for apheresis.

- Donors must be HIV negative, hepatitis B surface antigen negative, and hepatitis C
antibody negative.

DLI Control Subjects:

The DLI Control Subjects will serve as a comparison for Arm A, and eligibility criteria
are intended to enroll subjects who are similar with respect to allotransplant
characteristics.

- Patients must be 18 - 75 years of age.

- Patients who have received an allotransplant to treat malignancy and who are going to
receive an unmanipulated or stem-cell mobilized DLI to treat persistent tumor as part
of their treatment program on another NIH/CC protocol.

- ECOG performance status of less than or equal to 3 (Karnofsky performance status of
greater than or equal to 50%).

- Life expectancy greater than or equal to 1 month.

- Patients with minimal to no clinical evidence of acute GVHD (Grade 0-I) or mild-
chronic GVHD while off of systemic immunosuppressive therapy.

- Available source of clinical donor lymphocyte cell product, including a stem
cell-mobilized product.

- Patients whose related allotransplant donor is available, eligible and enrolled
on this or another NIH/CC protocol that permits collection of a clinical donor
lymphocyte cell product, and donors are first-degree relatives with genotypic
identity at 5-6/6 HLA loci (HLA- A, B, and DR. Haploidentical (less than 5/6
genotypic identity) allotransplant recipients will not be eligible, for
consistency with Arm A Subjects.

- Patients whose related or unrelated allotransplant donors are unavailable or
ineligible, but who have cryopreserved donor lymphocyte cell products available
for clinical use on this trial.

- Patients must have disease that has failed to respond after a minimum of four weeks
to:

- Evidence of complete donor-T cell engraftment (greater than 90% chimerism) of the
circulating T cells.

- A trial of tapering immunosuppressive therapy, including trials that are discontinued
due to development or flare of GVHD.

- Adequate venous access for peripheral apheresis, or consent to use a temporary
central venous catheter for apheresis or consent to a large-volume (70cc) blood draw.

- Permission from their treating transplant physician or designee to participate on
study.

- Ability to give informed consent.

EXCLUSION CRITERIA:

Treatment Subjects:

- Tumor-directed therapy within two weeks of DLI.

- Patients with rapid disease progression or aggressive tumor histology which, in the
opinion of the PI, is likely to require urgent therapy within 60 days in order to
preserve organ function or quality of life, and there is an available standard
therapy to which the patient has a reasonable chance of responding.

- Progressive disease that, in the opinion of the PI, requires urgent standard therapy,
e.g., threatened organ function, acceptable quality of life, etc.

- Uncontrolled GVHD, i.e., either acute GVHD Grade III or chronic-moderate/severe GVHD
that has not responded to the current dose of systemic therapy or any history of
steroid-refractory acute GVHD, Grade IV acute GVHD, or chronic-severe GVHD.

- Active infection that is not responding to antimicrobial therapy.

- Active psychiatric disorder which may compromise compliance with transplant protocol,
or which does not allow for appropriate informed consent (as determined by Principal
Investigator and/or her designee).

- Pregnant or lactating. Subjects of childbearing potential must use an effective
method of contraception. The effects of the immunosuppressive medications that could
be required to treat GHVD are likely to be harmful to a fetus. The effects upon
breast milk are also unknown and may be harmful to an infant.

- Absolute neutrophil count of less than 500 cells/?l. At the PI's discretion, patients
with marrow replacement by tumor as the probable etiology of an absolute neutrophil
count of less than 500 cells/microL may be eligible for enrollment.

- In order to prevent delay of potentially stabilizing palliative therapy, the
following conditions will exclude eligibility: untreated active leptomeningeal
involvement with malignancy, untreated brain metastasis, and other organ-threatening
diseases in which palliative treatment options with reasonable probability of
efficacy (15% or higher) are available. Patients with these conditions for whom
available palliative options have been tried or deemed unacceptable but who otherwise
meet eligibility criteria may, at the discretion of the PI, be considered for
enrollment.

Donor Subjects:

- History of a psychiatric disorder that the PI determines might compromise compliance
with transplant protocol, or that does not allow for appropriate informed consent.

- Hypertension that is not controlled by medication, history of stroke, or severe heart
disease (donors with symptomatic angina will be excluded). Donors with a history of
coronary artery bypass grafting or angioplasty who are symptom free will receive a
cardiology evaluation and be considered on a case-by-case basis.

- History of prior malignancy. However, cancer survivors who have undergone potentially
curative therapy and have had no evidence of that disease for at least 5 years may be
considered for lymphocyte donation on a case-by-case basis.

- Anemia (Hb less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000 per
ml). However, potential donors with Hb levels less than 11 gm/dl that is due to iron
deficiency will be eligible as long as the donor is initiated on iron replacement
therapy and the case is individually approved by NIH DTM.

- Pregnancy. Donor Subjects of childbearing potential must use an effective method of
contraception until after completion of apheresis. The effects of apheresis are
unknown to be safe to a fetus.

DLI Control Subjects:

- Tumor-directed therapy within two weeks of DLI.

- Uncontrolled GVHD

- Pregnant or lactating. Subjects of childbearing potential must use an effective
method of contraception until after completion of apheresis. The effects of apheresis
are unknown to be safe to a fetus.

- History of a psychiatric disorder that the PI determines might compromise compliance
with protocol, or that does not allow for appropriate informed consent.

- Hypertension that is not controlled by medication, history of stroke, or severe heart
disease (subjects with symptomatic angina will be excluded).