• Feasibility (defined as 11 of 15 tumors yielding 1.0 × 10e7 tumor-derived lymphocytes/kg meeting defined release criteria) [ Designated as safety issue: No ]
  
• Safety (defined as having no greater risk of developing acute graft-versus-host disease by day 28 as with standard therapy with unmanipulated donor lymphocyte infusion) [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• Determine the feasibility of administering ex vivo costimulated, expanded, clinically relevant numbers of tumor-derived lymphocytes (TDL) in patients with persistent or recurrent B-cell lymphoid malignancies after prior allogeneic hematopoietic stem cell transplantation (alloHSCT).
• Determine the safety of TDL, in terms of the incidence of infusion-related toxicities, hyperacute graft-versus-host disease (GVHD), or acute or chronic GVHD, in these patients.

Secondary

• Determine antitumor response in patients treated with TDL.
• Investigate methods of characterizing residual tumor after alloHSCT by evaluating patient tumor tissue samples for tumor viability and inflammatory infiltrate; assessing residual tumor cells for antigen specificity and gene expression; and assaying TDL for tumor reactivity and specificity.
• Investigate methods of characterizing the immune phenotypic and functional characteristics of patient TDL and tumor-selected TDL and compare the in vitro antitumor efficacy of these two cell products.
• Identify recombinant, graft-versus-tumor (GVT) antigens in tumor samples before and after administration of TDL to better understand the mechanisms and effectors of GVT response in these patients.
• Investigate methods of characterizing tumor infiltrate in these patients by evaluating tumor tissue samples for viability and inflammatory infiltrate; assessing residual tumor cells for enhanced antigen specificity and gene expression; and assaying TDL for tumor reactivity and specificity.
• Investigate the effect of immune depletion in these patients on the availability of homeostatic cytokines and the requirement for exogenous cytokine support of in-vivo survival and expansion of adoptively transferred cells.

OUTLINE: This is a pilot study.

Patients undergo apheresis to collect peripheral blood mononuclear cells (PBMCs). Patients then undergo surgical resection of accessible tumor.

Tumor-infiltrating T lymphocytes (TILs) are isolated from tumor tissue, costimulated with PBMCs, and expanded ex vivo to generate tumor-derived lymphocytes (TDLs). Beginning at least 24 days after surgery and within 7 days after tumor assessment, patients receive an infusion of TDL IV in the absence of disease progression or unacceptable toxicity.

Patients undergo blood, bone marrow, and tissue collection periodically during study for correlative studies, including the following: phenotypic and functional characterization of residual tumor and TDL by immunohistochemistry and fluorescent in situ hybridization; identification of prognostic markers of clinical outcome (i.e., HLA-A, -B, and -C; HLA-DR, Fas ligand, CD80, and CD86) by flow cytometry; in vitro assessment of tumor-reactive, selectively expanded T-cell clones by gene expression profiling; and evaluation of immune response by tumor-specific cytotoxicity assays (immunoenzyme techniques) and DNA sequencing for recombinant graft-versus-tumor antigens. Chimerism is assessed with a polymerase chain reaction-based assay and cytogenetics.

After completion of study therapy, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.