Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-5-18
pubmed:abstractText
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 MM 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 Vbeta gene subfamilies. This method determines the relative utilization of each Vbeta gene subfamily and also allows the identification of clonal and oligoclonal T cell populations through analysis of CDR3 regions for each TCR Vbeta 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 later 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0268-3369
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
623-32
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10734296-Adult, pubmed-meshheading:10734296-Bone Marrow Transplantation, pubmed-meshheading:10734296-Clone Cells, pubmed-meshheading:10734296-Complementarity Determining Regions, pubmed-meshheading:10734296-Female, pubmed-meshheading:10734296-Graft vs Host Disease, pubmed-meshheading:10734296-Graft vs Tumor Effect, pubmed-meshheading:10734296-Humans, pubmed-meshheading:10734296-Immunoglobulin Variable Region, pubmed-meshheading:10734296-Lymphocyte Transfusion, pubmed-meshheading:10734296-Male, pubmed-meshheading:10734296-Middle Aged, pubmed-meshheading:10734296-Multiple Myeloma, pubmed-meshheading:10734296-Receptors, Antigen, T-Cell, pubmed-meshheading:10734296-Receptors, Antigen, T-Cell, alpha-beta, pubmed-meshheading:10734296-T-Lymphocytes, pubmed-meshheading:10734296-Transplantation, Homologous
pubmed:year
2000
pubmed:articleTitle
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.
pubmed:affiliation
Center for Hematologic Oncology, Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Case Reports, Research Support, Non-U.S. Gov't, Multicenter Study