Pilot Study of Radiation-Enhanced Allogeneic Cell Therapy for Progressive Hematologic Malignancy After Allogeneic Hematopoietic Stem Cell Transplantation

* 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 National Cancer Institute (NCI)/Center for Cancer Research (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 graft versus host disease (GVHD) * Patients must be 18 - 75 years of age. * Eastern Cooperative Oncology Group (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 National Institutes of Health (NIH)/Clinical Center (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 human leukocyte antigen (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 donor lymphocyte infusion (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 Subjects 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 human immunodeficiency virus (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 National Institutes of Health (NIH)/Clinical Center (CC) protocol. * Eastern Cooperative Oncology Group (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 human leukocyte antigen (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 principal investigator (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/microL. At the PIs 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 (hemoglobin (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 Department of Transfusion Medicine (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).