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

Background: * The prognosis for patients with cancer who have relapsed or progressive disease after allogeneic hematopoietic stem cell transplantation (allotransplant) is poor. Effective therapies for patients who fail withdrawal of immune suppression and administration of donor lymphocyte infusions (DLI) have not been identified. * Increasing the efficacy of allotransplant without increasing toxicity is a major goal of transplantation research. A major research effort within the Experimental Transplantation and Immunobiology Branch (ETIB) is to identify ways to build on the allogeneic platform to treat relapse after allotransplant. * We hypothesize that a single fraction of radiation to tumor prior to administration of donor lymphocytes will increase the potency of systemic graft-versus-tumor (GVT) effects without increasing graft-versus-host disease (GVHD). Objectives: \- To determine the safety, in relation to GVHD and allograft function, and efficacy, in terms of systemic tumor response, of administering single-fraction, targeted radiotherapy with or without DLI to patients with persistent tumor after allotransplant. Eligibility: * Adults with hematologic malignancies that progress or recur after allotransplant, successful donor T cell engraftment, and trial of withdrawal of immune suppression. * Disease that is amenable to radiation as well as additional measurable disease outside the radiation field. * Subjects with treatment-refractory acute or chronic GVHD will not be eligible. Design: * Subjects will receive radiation in a single, 8-Gy fraction to sites of disease. At least one site of measurable disease will remain untreated with radiation for evaluation of systemic response. * There will be two arms. Arm A will include subjects with available donor lymphocytes and who have not had GVHD requiring systemic treatment; they shall receive a DLI the day after completion of radiation. Arm B will include those who have previously required systemic therapy for GVHD, are at high risk of significant GVHD, and/or who do not have available donor lymphocytes; they shall receive radiation without DLI. * Additional disease that is outside the field of radiation will be monitored for systemic effects of the therapy. * Subjects will be monitored on an outpatient basis for the development or exacerbation of GVHD, excessive hematologic toxicity or other toxicity from radiation, and for tumor responses for at least 60 days. * Enrollment: * Treatment Subjects: The protocol will treat 21 subjects per arm (total 42). There are stopping rules after 8 and 15 patients per arm for excessive GVHD or radiation toxicity. * DLI Control Subjects; 15 control subjects who receive DLI for persistent disease as part of their care on another National Institutes of Health (NIH) protocol, will be included to compare the immunologic effects of radiation followed by DLI (Arm A) with DLI alone. * Donor Subjects: Related donors of Arm A Treatment Subjects and DLI Control Subjects will be enrolled for collection of clinical DLI product, a portion of which will be used for research (up to 36 Donor Subjects).