Significant Changes in Inducible Cytokine Synthesis by Activated Peripheral Blood Leukocytes of Multiple Myeloma Patients Receiving Standard Dose Autologous Stem Cell Transplantation

• Published in: Blood 2011-11, Vol.118 (21), p.5096-5096
• Main Authors: Lee, Bang-Ning, Shah, Nina, Giralt, Sergio, Gao, Hui, Cohen, Evan N, Williams, Lori, Gning, Ibrahima, Mendoza, Tito R, Brown, Jane O, Johnson, Valen E, Champlin, Richard, Cleeland, Charles S, Reuben, James M
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.5096.5096

Abstract 5096 Multiple myeloma (MM) is an incurable cancer characterized by the clonal proliferation of plasma cells within the bone marrow. We previously reported a positive correlation between serum levels of inflammatory cytokines and the severity of the self-reported symptoms in MM patients undergoing high dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). As cytokines produced by activated peripheral blood (PB) leukocytes are likely to increase the severity of self-reported symptoms, we determined the ability of PB CD4+ and CD8+ T-lymphocytes, and CD14+ monocytes to produce cytokines following activation through the T-cell receptor (TCR) with anti-CD3 antibodies and toll-like receptor-4 with lipopolysaccharide (LPS), respectively. We studied 24 patients (65 yrs ± 7 yrs) with Durie-Salmon stages II/III MM, 15 men and 9 women; 18 Caucasian, 2 Hispanic, and 3 African-American and 1 Asian. All patients were part of an ongoing clinical trial studying high versus standard dose of autologous stem cells (AutoSC) during HDC followed by auto-SCT. All patients received standard high dose melphalan (200 mg/m2 in 2 divided doses) as their myeloablative chemotherapy. Fourteen subjects received a standard dose (SD) of AutoSC (4–6×106 CD34+ cells/kg) and 10 patients received a high dose (HD) of AutoSC (10–15×106 CD34+ cells/kg). The ability of TCR-activated CD4+ and CD8+ T cells to synthesize cytokines (Th1: IL-2, TNF-α, and IFN-γ; Th2: IL-4, and IL-10) and LPS-activated monocytes to synthesize IL-1β, IL-6, IL-8, IL-12, MCP-1, and TNF-a was assessed prior to auto-SCT and thereafter at 2 weeks, 1, 2, 6 and 12 months by multi-color flow cytometry assays. Friedman test was used to determine the differences in the percentages of cytokine-producing cells by each cohort across time. Wilcoxon tests were used as follow-up tests to determine at which time the differences exist. Mann-Whitney test was used to determine if there were differences in the percentages of leukocytes producing cytokines in patients who received SD or the HD of AuSC. The SD AuSC cohort had significant changes in the mean ± SEM percentages of TCR-activated CD3+CD8+ T cells that produced IL-2 and of CD3+CD4+ T cells that produced IL-10 across time. The increase in percentage of IL-2-producing T cells was followed by a significant decline (when compared with baseline) at 1-month post auto-SCT (14.5% ± 3.7% vs. 4.5% ± 1.3%; P = 0.019). This decline was sustained throughout the 12-