Adoptive Cell Therapy for B-Cell Cancers in Patients After Stem Cell Transplantation

Background: * The prognosis for patients with B-cell lymphoid malignancies (BCL) with relapse or refractory disease after allogeneic hematopoietic stem cell transplantation (AlloHSCT) is poor. Effective therapy for patients who fail withdrawal of immune suppression and administration of donor lymphocyte infusions (DLI) has not been identified. * In the setting of recurrent or refractory BCL, the immunologic graft-versus-tumor (GVT) effect generated by unmanipulated donor lymphocytes is often not durable and can be accompanied by graft-versus-host disease (GVHD). * We have hypothesized that lymphocytes found in tumor after alloHSCT are of donor origin, and because they are tumor-derived, they may be tumor-specific in their homing and antigen specificity characteristics. Similarly, inpatients with bone marrow involvement with tumor, the marrow may be enriched with similarly tumor-specific T cells. Further, activation and expansion of these cells through CD3/CD28 costimulation may yield a more effective form of cell therapy than DLI after alloHSCT, with enhanced GVT effects and less GVHD. Objectives: * To evaluate the feasibility of isolating and expanding clinically relevant numbers of TDL from patients after alloHSCT. * To determine the safety, vis-a-vis infusion toxicities and/or GVHD, of administering TDL. Eligibility: * Adults with B cell malignancies with tumor that has not responded to successful T cell engraftment after alloHSCT, withdrawal of immune suppression and administration of donor lymphocyte infusion will be eligible for this trial. * Subjects must have a minimum of 1.5 cm of accessible tumor which is amenable to resection with minimal surgical morbidity and/or bone marrow tumor involvement. Design: * Subjects will have accessible lesion surgically resected and/or harvested via bone marrow aspiration. * Lymphocytes will be liberated and expanded using a co-stimulatory approach with anti-CD3/CD28 magnetic beads to generate TDL and/or marrow-TDL. * 1.0 x 10(6) - 1.0 x 10(8) TDL will be administered. * Subjects will be monitored for the development of infusion reactions (in-hospital for 24 hours after infusion), GVHD (weekly for four weeks then monthly) and tumor responses (monthly). * Two cohorts will be enrolled, with an arm evaluating TDL from resected tumor and an arm to evaluate marrow-TDL from tumor-involved bone marrow. For the TDL arm, 15 to 18 patients and up to 18 donors will be enrolled; for the marrow-TDL arem, 15 patients and up to 15 donors will be enrolled. Both arms will test the primary endpoints of feasibility (with at least 11 of 15 tumors yielding 1.0 x 10(6) TDL/kg meeting defined release criteria) and safety (primarily defined as having a no greater risk of developing grade II-IV acute GVHD by day 28 as standard therapy with unmanipulated DLI).