title: Antigen-specific T-cell immunity in multiple myeloma patients is restored following high-dose therapy: implications for timing of vaccination.
abstract: The present study analyses the influence of high-dose chemotherapy (HD) and autologous stem cell transplantation on natural and vaccine induced specific immunity in multiple myeloma patients. Peripheral blood was collected from six multiple myeloma (MM) patients at serial time points in connection with treatment and during a follow-up period of 3 months. T-cell response to cytomegalovirus (CMV), varicella zoster virus (VZV) and tetanus toxoid (TT) was determined by flow cytometry analysis for CD69, TNFalpha, IFNgamma, IL-4 expression and cell proliferation. At diagnosis and prior to induction chemotherapy TNFalpha expressing T cells in 5/6 patients were found specific for CMV, 3/6 for VZV and 4/6 for TT. Serial analyses during treatment conclude impaired immune response, however, 3 months post-transplantation all but one patient had regained cytokine expressing CD8(+) T cells specific for CMV, VZV and TT. The highest percentages of cytokine responding T cells were observed after stimulation with CMV antigen. A striking observation was the low cytokine reactivity (close to zero) measured in G-CSF mobilized blood at the time of leukapheresis. In spite of a general reduction of the CD4/CD8 ratio following transplantation, recovery of antigen specific CD4(+) T cells reactivity generally occurred prior to CD8(+) recovery and often to a higher level. In conclusion, the study demonstrates that natural as well as vaccine induced specific immunity present prior to HD was regained after stem cell transplantation, hence identifying a possible window for future vaccination trials.
authors.affiliation: Center for Cancer Immune Therapy, Department of Haematology, Copenhagen University Hospital, Herlev, Denmark. inge.m.svane@dadlnet.dk
authors.forename: I M
authors.initials: IM
authors.lastname: Svane
authors.forename: K
authors.initials: K
authors.lastname: Nikolajsen
authors.forename: H E
authors.initials: HE
authors.lastname: Johnsen
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D013745:Tetanus Toxoid; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin