title: Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma.
abstract: Reconstitution of T-cell immunity after bone marrow transplantation (BMT) is often delayed, resulting in a prolonged period of immunodeficiency. Donor lymphocyte infusion (DLI) has been used to enhance graft-versus-leukemia activity after BMT, but the effects of DLI on immune reconstitution have not been established. We studied 9 patients with multiple myeloma who received myeloablative therapy and T-cell-depleted allogeneic BMT followed 6 months later by infusion of lymphocytes from the same donor. DLI consisted of 3 x 10(7) CD4(+) donor T cells per kilogram obtained after in vitro depletion of CD8(+) cells. Cell surface phenotype of peripheral lymphocytes, T-cell receptor (TCR) V beta repertoire, TCR rearrangement excision circles (TRECs), and hematopoietic chimerism were studied in the first 6 months after BMT and for 1 year after DLI. These studies were also performed in 7 patients who received similar myeloablative therapy and BMT but without DLI. Phenotypic reconstitution of T and natural killer cells was similar in both groups, but patients who received CD4(+) DLI developed increased numbers of CD20(+) B cells. TCR V beta repertoire complexity was decreased at 3 and 6 months after BMT but improved more rapidly in patients who received DLI (P =.01). CD4(+) DLI was also associated with increased numbers of TRECs in CD3(+) T cells (P <.001) and with conversion to complete donor hematopoiesis (P =.05). These results provide evidence that prophylactic infusion of CD4(+) donor lymphocytes 6 months after BMT enhances reconstitution of donor T cells and conversion to donor hematopoiesis as well as promoting antitumor immunity.
authors.affiliation: Center for Hematologic Oncology and Department of Biostatistics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bellucci
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.forename: Antoinette
authors.initials: A
authors.lastname: Chillemi
authors.forename: Ephraim
authors.initials: E
authors.lastname: Hochberg
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Wu
authors.forename: Christine
authors.initials: C
authors.lastname: Canning
authors.forename: Robert
authors.initials: R
authors.lastname: Schlossman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000254:growth & development; D016130:Immunophenotyping; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000276:immunology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods; D016896:Treatment Outcome
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta