The applicant's primary hypothesis is that the T cell component of the immune response will be important in the induction of a clinical response to donor lymphocyte infusions (DLI) in multiple myeloma (MM). It is important to characterize the T cell compartments that may contribute to the response and also to evaluate approaches that promote their reactivity to the myeloma clone. In relapsed post-allo-bone marrow transplantation (BMT) patients entering the ECOG phase II DLI clinical protocol (E1A97), the source of tumor antigen remains and can still serve to stimulate donor T cells. Study of MM patients' T cell antimyeloma functions, T cell phenotype, blood idiotype-specific T cells and T cell repertoire post-allo-BMT but prior to DLI will tell us about their baseline immune status. Sequential T cell studies after the DLI will be informative for any amplification of the cellular immune response, and stability of that amplification. Additional comparisons between the changes in blood T cell parameters and changes in the level of clonal B cells measured by the MIg response, by flow cytometry, and by PCR will enable the applicant to examine any association between T cell reactivity and clinical response. This application is designed to provide a unique laboratory investigation of the immune T cell status of MM patients. Since the evidence is incomplete regarding the clinical importance of the T cells to the growth and viability of the malignant clone after DLI, the applicant will utilize the DLI clinical protocol to help better define the relevant donor T cell immune component in MM patients. In addition, he will identify patient subsets on the basis of their immune T cell response, who may be more responsive to the new approach of post-Allo BMT DLI treatment. Finally, if DLI is found to be associated with both a T cell response and clinically significant responses he will have improved insight into the mechanism of DLI efficacy.
