Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma.
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.
Bellucci
Roberto
R
Center for Hematologic Oncology and Department of Biostatistics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Alyea
Edwin P
EP
Weller
Edie
E
Chillemi
Antoinette
A
Hochberg
Ephraim
E
Wu
Catherine J
CJ
Canning
Christine
C
Schlossman
Robert
R
Soiffer
Robert J
RJ
Anderson
Kenneth C
KC
Ritz
Jerome
J
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
D016693:Receptors, Antigen, T-Cell, alpha-beta