Expansion of an Immunophenotypically Distinct Cytotoxic T-Cell Population Following Autologous Stem Cell Transplant in Plasma Cell Myeloma.
Kristy Wolniak, Charles Goolsby, Dave Dittman, Laura Marszalek, Seema Singhal, Jayesh Mehta, LoAnn C Peterson. Feinberg School of Medicine, Northwestern University, Chicago, IL
Background: Following autologous stem cell transplant with high dose chemotherapy in plasma cell myeloma patients, an increased proportion of large granular lymphocytes (LGL) has been observed in restaging bone marrow samples. We propose that this population of LGLs represents a benign expansion of a distinct subset of cytotoxic T cells which occurs following autologous stem cell transplant.
Design: To assess frequency and phenotype of the CD8+ T cells, flow cytometric analysis was performed on 51 bone marrow aspirates sent for myeloma evaluation and 8 controls. Additionally, morphologic assessment results and clinical data were collected on the patients including disease stage and response, engraftment, and infectious complications. To assess for clonal T cell populations, molecular analysis was performed on a subset of the bone marrow aspirates and killer inhibitory receptor (KIR) restriction was assessed by flow cytometry. ANOVA and t-test analyses were performed with SPSS.
Results: Directly post-transplant (N=20), patients had a significant increase in the proportion of CD8+ T-cells (71±11%) as compared to controls (37.8±12.5%, p<.005). Of note, patients beyond 6 months past transplant continued to have a persistent expansion of this population (55±12.6% p<.01). This expanded population has a distinct phenotype with expression of CD3 and TIA-1, variable CD57 expression, negative to dim CD56, and no expression of CD16. In most patients, no KIR restriction or loss of T-cell antigens is identified. Monoclonal TCR gene rearrangements were identified in several myeloma patient samples including patients with and without transplant. Interestingly, one post-transplant patient had a clearly identified and persistent subset of CD8+CD56+ T cells with an abnormal loss of CD5 and with KIR restriction. This patient as well as all other patients assessed had good engraftment and no persistent neutropenia. The level of CD8+ cell expansion did not correlate with engraftment, myeloma disease response to transplant, or to infectious complications.
Conclusions: In post-transplant myeloma patients, there is an expansion of a distinct cytotoxic T cell population. Although there is evidence of both clonality and persistence of this cytotoxic population, no clinical evidence of a neoplastic T-cell process was identified. Further studies are necessary to elucidate the function of this distinct population of T cells.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 232, Tuesday Morning