Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host disease in patients with relapsed multiple myeloma after donor lymphocyte infusion

被引:48
作者
Orsini, E
Alyea, EP
Schlossman, R
Canning, C
Soiffer, RJ
Chillemi, A
Neuberg, D
Anderson, KC
Ritz, J
机构
[1] Dana Farber Canc Inst, Ctr Hematol Oncol, Dept Adult Oncol, Boston, MA 02115 USA
[2] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA
关键词
multiple myeloma; donor lymphocyte infusions; graft-versus-myeloma; GVHD; V beta repertoire;
D O I
10.1038/sj.bmt.1702187
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Recent reports of clinical responses following donor lymphocyte infusions (DLI) in patients with relapsed multiple myeloma (MM) after allogeneic BMT have demonstrated the ability of allogeneic cells to mediate a graft-versus-myeloma (GVM) effect, but the mechanisms involved have not been determined. To identify changes in the T cell compartment associated with DLI, we performed a molecular analysis of the T cell receptor (TCR) repertoire in four patients with relapsed MR I who received infusions of CD4(+) lymphocytes from HLA-identical sibling donors. Three of the four patients demonstrated a clinical anti-myeloma response following DLI but also developed graft-versus-host disease (GVHD). The TCR repertoire was examined after PCR amplification of 24 VP gene subfamilies. This method determines the relative utilization of each V beta gene subfamily and also allows the identification of clonal and oligoclonal T cell populations through analysis of CDR3 regions for each TCR V beta gene subfamily. Serial blood samples were obtained over at least a 1 year period before and after DLI and results compared to 10 normal donors. Serial analysis of CDR3 size profiles demonstrated the appearance of clonal T cell populations after DLI in each of the three responding patients. The appearance of some clones was noted within the first 3 months after DLI and coincided with decreasing levels of monoclonal paraprotein indicating an ongoing GVM response. Other T cell clones appeared at Inter time points and coincided with the development of GVHD. These findings demonstrate that T cell clones with different patterns of onset can be identified in the peripheral blood of MM patients following DLI. Further functional characterization of these distinct clonal expansions will be required to determine whether these T cell clones are mediators of either anti-myeloma or anti-host activity.
引用
收藏
页码:623 / 632
页数:10
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