The prognostic significance of T cell receptor beta gene rearrangements and idiotype-reactive T cells in multiple myeloma.
Clonal T cell populations with idiotype specificity are present in the peripheral blood of a proportion of patients with multiple myeloma. We have identified the presence of both T cell subpopulations with a specificity for autologous immunoglobin fragments and T cell receptor beta gene rearrangements in peripheral blood samples of patients with myeloma. T cell receptor beta gene rearrangements were detected in 38 of 119 patient samples (32%) and were more common in progressive disease (70%), than at diagnosis (25%) or in stable disease (23%). The 38 patients who had T cell receptor beta gene rearrangements detected at any time had a better overall survival (median not yet achieved) than the patients who never had rearrangements detected (median 45 months, n = 49; chi2 = 6.2, P < 0.01). All 12 patients with T cell receptor beta gene rearrangements at diagnosis are still alive whereas the median survival for 28 patients with a germline configuration at diagnosis was 40 months (chi2 = 5.8, P > 0.01). The presence of T cell receptor beta gene rearrangements even conferred a survival advantage during progressive disease (median survival 44 months vs 19 months; chi2 = 8.7, P < 0.003). Two colour flow cytometry with biotinylated autologous immunoglobulin fragments demonstrated idiotype-reactive T cells in the peripheral blood of five out of 15 patients all of whom had T cell gene rearrangements. The remaining 10 patients had neither idiotype-reactive T cells nor a detectable T cell receptor beta gene rearrangement in concurrent samples. Thus in patients with myeloma there was a good correlation between the presence of T cell receptor beta gene rearrangements and idiotype-reactive T cells. Patients with a rearranged T cell receptor beta gene had a significantly better prognosis.
Brown
R D
RD
Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Yuen
E
E
Nelson
M
M
Gibson
J
J
Joshua
D
D
D000368:Aged; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007111:Immunity, Cellular; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008137:Longitudinal Studies; D009101:Multiple Myeloma / Q000235:genetics*; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*
D007130:Immunoglobulin Idiotypes; D016693:Receptors, Antigen, T-Cell, alpha-beta